20 results on '"*SENSORY receptors"'
Search Results
2. Activation of retinal glial (Müller) cells by extracellular ATP induces pronounced increases in extracellular H+ flux
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Michael Gongwer, Robert Paul Malchow, Boriana K. Tchernookova, Matthew A. Kreitzer, Jason Jacoby, David Swygart, Lexi Shepherd, Ryan Kaufman, Marin Young, Hannah Caringal, and Chad Heer
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0301 basic medicine ,Photoreceptors ,P2Y receptor ,Caudata ,Sensory Receptors ,lcsh:Medicine ,Social Sciences ,4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ,Ambystoma ,Biochemistry ,chemistry.chemical_compound ,0302 clinical medicine ,Adenosine Triphosphate ,Cell Signaling ,Animal Cells ,Medicine and Health Sciences ,Psychology ,Skates, Fish ,lcsh:Science ,Uncategorized ,Neurons ,Multidisciplinary ,Physics ,Lampreys ,Eukaryota ,Neurochemistry ,Neurotransmitters ,Hydrogen-Ion Concentration ,Adenosine Diphosphate ,Chemistry ,Pyridoxal Phosphate ,Receptors, Purinergic P2Y ,Physical Sciences ,Vertebrates ,Engineering and Technology ,Sensory Perception ,Signal transduction ,Anatomy ,Cellular Types ,Glutamate ,Protons ,Intracellular ,Signal Transduction ,Research Article ,Thapsigargin ,Ocular Anatomy ,Ependymoglial Cells ,Suramin ,In Vitro Techniques ,Retina ,Amphibians ,03 medical and health sciences ,Ocular System ,Extracellular ,Animals ,Humans ,PPADS ,Calcium Signaling ,Salamanders ,Electrodes ,Ion transporter ,Nuclear Physics ,Nucleons ,Ion Transport ,lcsh:R ,Chemical Compounds ,Organisms ,Bicarbonate transport ,Biology and Life Sciences ,Afferent Neurons ,Extracellular Fluid ,Cell Biology ,Macaca mulatta ,Rats ,Ictaluridae ,Macaca fascicularis ,Bicarbonates ,030104 developmental biology ,chemistry ,Cellular Neuroscience ,Biophysics ,lcsh:Q ,sense organs ,Electronics ,Microelectrodes ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Small alterations in extracellular acidity are potentially important modulators of neuronal signaling within the vertebrate retina. Here we report a novel extracellular acidification mechanism mediated by glial cells in the retina. Using self-referencing H+-selective microelectrodes to measure extracellular H+ fluxes, we show that activation of retinal Müller (glial) cells of the tiger salamander by micromolar concentrations of extracellular ATP induces a pronounced extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non-hydrolyzable analog ATPγs at micromolar concentrations were also potent stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting activation of P2Y receptors. Bath-applied ATP induced an intracellular rise in calcium in Müller cells; both the calcium rise and the extracellular H+ fluxes were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by thapsigargin and when the PLC-IP3 signaling pathway was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also markedly reduced the ATP-induced increase in H+ flux while SITS had no effect. ATP-induced H+ fluxes were also observed from Müller cells isolated from human, rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily conserved mechanism of potential general importance. Extracellular ATP also induced significant increases in extracellular H+ flux at the level of both the outer and inner plexiform layers in retinal slices of tiger salamander which was significantly reduced by suramin and PPADS. We suggest that the novel H+ flux mediated by ATP-activation of Müller cells and of other glia as well may be a key mechanism modulating neuronal signaling in the vertebrate retina and throughout the brain.
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- 2022
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3. The involvement of type IV pili and the phytochrome CphA in gliding motility, lateral motility and photophobotaxis of the cyanobacterium Phormidium lacuna
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Lamparter, T., Babian, J., Frohlich, K., Mielke, M., Weber, N., Wunsch, N., Zais, F., Schulz, K., Aschmann, V., Spohrer, N., and Krau��, N.
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Photoreceptors ,Sensory Receptors ,Light ,Social Sciences ,Pathology and Laboratory Medicine ,Biochemistry ,Animal Cells ,Medicine and Health Sciences ,Psychology ,Neurons ,Physics ,Electromagnetic Radiation ,Phormidium ,Phototaxis ,Synechocystis ,Genomics ,Physical Sciences ,Medicine ,Sensory Perception ,Phytochrome ,Pathogens ,Cellular Types ,Cellular Structures and Organelles ,Research Article ,Signal Transduction ,Pathogen Motility ,Life sciences ,biology ,Virulence Factors ,Science ,Cyanobacteria ,Bacterial Proteins ,Protein Domains ,ddc:570 ,Genetics ,Bacteriological Techniques ,Bacteria ,Organisms ,Cognitive Psychology ,Biology and Life Sciences ,Afferent Neurons ,Proteins ,Cell Biology ,Pili and Fimbriae ,Fimbriae, Bacterial ,Cellular Neuroscience ,Mutation ,Cognitive Science ,Perception ,Neuroscience - Abstract
Phormidium lacuna is a naturally competent, filamentous cyanobacterium that belongs to the order Oscillatoriales. The filaments are motile on agar and other surfaces and display rapid lateral movements in liquid culture. Furthermore, they exhibit a photophobotactic response, a phototactic response towards light that is projected vertically onto the area covered by the culture. However, the molecular mechanisms underlying these phenomena are unclear. We performed the first molecular studies on the motility of an Oscillatoriales member. We generated mutants in which a kanamycin resistance cassette (KanR) was integrated in the phytochrome gene cphA and in various genes of the type IV pilin apparatus. pilM, pilN, pilQ and pilT mutants were defective in gliding motility, lateral movements and photophobotaxis, indicating that type IV pili are involved in all three kinds of motility. pilB mutants were only partially blocked in terms of their responses. pilB is the proposed ATPase for expelling of the filament in type IV pili. The genome reveals proteins sharing weak pilB homology in the ATPase region, these might explain the incomplete phenotype. The cphA mutant revealed a significantly reduced photophobotactic response towards red light. Therefore, our results imply that CphA acts as one of several photophobotaxis photoreceptors or that it could modulate the photophobotaxis response.
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- 2022
4. Natural image statistics for mouse vision
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Luca Abballe and Hiroki Asari
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Photoreceptors ,Sensory Receptors ,genetic structures ,Light ,Vision ,Social Sciences ,Mice ,Animal Cells ,Medicine and Health Sciences ,Psychology ,Neurons ,Multidisciplinary ,Physics ,Electromagnetic Radiation ,Cameras ,Cone Opsins ,Optical Equipment ,Physical Sciences ,Retinal Cone Photoreceptor Cells ,Medicine ,Engineering and Technology ,Sensory Perception ,Anatomy ,Cellular Types ,Research Article ,Signal Transduction ,Imaging Techniques ,Science ,Ocular Anatomy ,Equipment ,Research and Analysis Methods ,Retina ,Ocular System ,Ultraviolet Radiation ,Animals ,Vision, Ocular ,Color Vision ,Cognitive Psychology ,Rod Opsins ,Biology and Life Sciences ,Afferent Neurons ,Optics ,Cell Biology ,eye diseases ,Cellular Neuroscience ,Cognitive Science ,Perception ,sense organs ,Photic Stimulation ,Neuroscience - Abstract
The mouse has dichromatic color vision based on two different types of opsins: short (S)- and middle (M)-wavelength-sensitive opsins with peak sensitivity to ultraviolet (UV; 360 nm) and green light (508 nm), respectively. In the mouse retina, cone photoreceptors that predominantly express the S-opsin are more sensitive to contrasts and denser towards the ventral retina, preferentially sampling the upper part of the visual field. In contrast, the expression of the M-opsin gradually increases towards the dorsal retina that encodes the lower visual field. Such a distinctive retinal organization is assumed to arise from a selective pressure in evolution to efficiently encode the natural scenes. However, natural image statistics of UV light remain largely unexplored. Here we developed a multi-spectral camera to acquire high-quality UV and green images of the same natural scenes, and examined the optimality of the mouse retina to the image statistics. We found that the local contrast and the spatial correlation were both higher in UV than in green for images above the horizon, but lower in UV than in green for those below the horizon. This suggests that the dorsoventral functional division of the mouse retina is not optimal for maximizing the bandwidth of information transmission. Factors besides the coding efficiency, such as visual behavioral requirements, will thus need to be considered to fully explain the characteristic organization of the mouse retina.
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- 2022
5. The Drosophila functional Smad suppressing element fuss, a homologue of the human Skor genes, retains pro-oncogenic properties of the Ski/Sno family
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Rass, Mathias, Gizler, Laura, Bayersdorfer, Florian, Irlbeck, Christoph, Schramm, Matthias Josef, and Schneuwly, Stephan
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Photoreceptors ,Cell signaling ,Life Cycles ,Sensory Receptors ,Social Sciences ,590 Tiere (Zoologie) ,Larvae ,Transforming Growth Factor beta ,Animal Cells ,Breast Tumors ,Medicine and Health Sciences ,Morphogenesis ,Drosophila Proteins ,Psychology ,Neurons ,Multidisciplinary ,Intracellular Signaling Peptides and Proteins ,Nuclear Proteins ,Signaling cascades ,Cell Differentiation ,Drosophila melanogaster ,Imaginal Discs ,Oncology ,DPP signaling cascade ,Medicine ,Sensory Perception ,Anatomy ,Cellular Types ,Signal Transduction ,Research Article ,Signal Inhibition ,animal structures ,Science ,Nerve Tissue Proteins ,Research and Analysis Methods ,Ocular System ,Proto-Oncogene Proteins ,Breast Cancer ,Animals ,Molecular Biology Techniques ,Molecular Biology ,Cell Proliferation ,Cognitive Psychology ,Biology and Life Sciences ,Afferent Neurons ,Cancers and Neoplasms ,Oncogenes ,Cell Biology ,Cellular Neuroscience ,ddc:590 ,Eyes ,Cognitive Science ,Perception ,Head ,Acyltransferases ,Transcription Factors ,Cloning ,Developmental Biology ,Neuroscience - Abstract
Over the years Ski and Sno have been found to be involved in cancer progression e.g. in oesophageal squamous cell carcinoma, melanoma, oestrogen receptor-positive breast carcinoma, colorectal carcinoma, and leukaemia. Often, their prooncogenic features have been linked to their ability of inhibiting the anti-proliferative action of TGF-ß signalling. Recently, not only pro-oncogenic but also anti-oncogenic functions of Ski/Sno proteins have been revealed. Besides Ski and Sno, which are ubiquitously expressed other members of Ski/Sno proteins exist which show highly specific neuronal expression, the SKI Family Transcriptional Corepressors (Skor). Among others Skor1 and Skor2 are involved in the development of Purkinje neurons and a mutation of Skor1 has been found to be associated with restless legs syndrome. But neither Skor1 nor Skor2 have been reported to be involved in cancer progression. Using overexpression studies in the Drosophila eye imaginal disc, we analysed if the Drosophila Skor homologue Fuss has retained the potential to inhibit differentiation and induce increased proliferation. Fuss expressed in cells posterior to the morphogenetic furrow, impairs photoreceptor axon pathfinding and inhibits differentiation of accessory cells. However, if its expression is induced prior to eye differentiation, Fuss might inhibit the differentiating function of Dpp signalling and might maintain proliferative action of Wg signalling, which is reminiscent of the Ski/Sno protein function in cancer.
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- 2022
6. Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a Drosophila model of Parkinson’s disease
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Victor, Girard, Florence, Jollivet, Oskar, Knittelfelder, Marion, Celle, Jean-Noel, Arsac, Gilles, Chatelain, Daan M, Van den Brink, Thierry, Baron, Andrej, Shevchenko, Ronald P, Kühnlein, Nathalie, Davoust, Bertrand, Mollereau, Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Unité Maladies Neuro-Dégénératives (MND), Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), and Karl-Franzens-Universität Graz
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Photoreceptors ,Sensory Receptors ,Hydrolases ,[SDV]Life Sciences [q-bio] ,MESH: Neurons ,Social Sciences ,QH426-470 ,Biochemistry ,Animals, Genetically Modified ,Neuroblastoma ,Animal Cells ,Medicine and Health Sciences ,Drosophila Proteins ,Psychology ,Lipases ,Parkinson ,MESH: Lipid Metabolism ,Neurons ,Drosophila Melanogaster ,Hydrolysis ,Chemical Reactions ,Eukaryota ,Parkinson Disease ,Animal Models ,Proteases ,Lipids ,Enzymes ,Insects ,Chemistry ,Experimental Organism Systems ,Physical Sciences ,alpha-Synuclein ,Sensory Perception ,Drosophila ,Cellular Types ,Anatomy ,Research Article ,Signal Transduction ,Arthropoda ,MESH: Drosophila Proteins ,Lipolysis ,Ocular Anatomy ,Research and Analysis Methods ,Protein Aggregation, Pathological ,MESH: Lipid Droplets ,Perilipin-2 ,Retina ,MESH: Animals, Genetically Modified ,Model Organisms ,Ocular System ,MESH: alpha-Synuclein ,Genetics ,Animals ,Humans ,Cognitive Psychology ,Organisms ,Membrane Transport Proteins ,Biology and Life Sciences ,Afferent Neurons ,Proteins ,Lipid Droplets ,Cell Biology ,Lipid Metabolism ,Invertebrates ,Disease Models, Animal ,Cellular Neuroscience ,Proteolysis ,Animal Studies ,Enzymology ,Cognitive Science ,Perception ,Zoology ,Entomology ,MESH: Parkinson Disease ,Neuroscience - Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein (αSyn) aggregation and associated with abnormalities in lipid metabolism. The accumulation of lipids in cytoplasmic organelles called lipid droplets (LDs) was observed in cellular models of PD. To investigate the pathophysiological consequences of interactions between αSyn and proteins that regulate the homeostasis of LDs, we used a transgenic Drosophila model of PD, in which human αSyn is specifically expressed in photoreceptor neurons. We first found that overexpression of the LD-coating proteins Perilipin 1 or 2 (dPlin1/2), which limit the access of lipases to LDs, markedly increased triacylglyclerol (TG) loaded LDs in neurons. However, dPlin-induced-LDs in neurons are independent of lipid anabolic (diacylglycerol acyltransferase 1/midway, fatty acid transport protein/dFatp) and catabolic (brummer TG lipase) enzymes, indicating that alternative mechanisms regulate neuronal LD homeostasis. Interestingly, the accumulation of LDs induced by various LD proteins (dPlin1, dPlin2, CG7900 or KlarsichtLD-BD) was synergistically amplified by the co-expression of αSyn, which localized to LDs in both Drosophila photoreceptor neurons and in human neuroblastoma cells. Finally, the accumulation of LDs increased the resistance of αSyn to proteolytic digestion, a characteristic of αSyn aggregation in human neurons. We propose that αSyn cooperates with LD proteins to inhibit lipolysis and that binding of αSyn to LDs contributes to the pathogenic misfolding and aggregation of αSyn in neurons., Author summary Parkinson’s disease (PD) is a neurodegenerative disease characterized by the neurotoxic aggregation of the alpha-synuclein (αSyn) protein. Cellular models of the disease are also associated with an abnormal fat storage in the form of lipid droplets (LDs). However, in which cells, neuron or glial cells, LDs accumulate in the organism remains unknown. To understand the relationship between αSyn and the accumulation of LDs, we used a Drosophila (fruit fly) model of PD. We found that, in the presence of a protein that coats LDs, perilipin, LDs accumulate in photoreceptor neurons of the fly. Interestingly, the accumulation of LDs induced by perilipin or other LD-coating proteins was enhanced in the presence of αSyn. Using human neuronal cell lines and the fly, we could show that LD-coating and αSyn proteins localize at the surface of LDs. Finally, we observed that the process of αSyn aggregation was enhanced in the presence of LDs by using a biochemical approach. We thus propose that the association of αSyn with LDs could contribute to αSyn aggregation and progression of the pathology.
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- 2021
7. Age-related changes of color visual acuity in normal eyes
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Sho Yokoyama, Takashi Kojima, Rie Horai, Hideki Nakamura, Hiroyuki Sato, Yoshiki Tanaka, Yukihito Kato, Mari Mitamura, Kazuo Ichikawa, and Kiyoshi Tanaka
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Photoreceptors ,Male ,Aging ,Visual acuity ,Sensory Receptors ,Light ,Spatial discrimination ,Vision ,Visual Acuity ,Social Sciences ,Standard deviation ,Animal Cells ,Medicine and Health Sciences ,Psychology ,Prospective Studies ,Neurons ,Multidisciplinary ,Eye Lens ,Physics ,Electromagnetic Radiation ,Middle Aged ,Physical Sciences ,Retinal Cone Photoreceptor Cells ,Medicine ,Sensory Perception ,Female ,medicine.symptom ,Anatomy ,Cellular Types ,Research Article ,Signal Transduction ,Adult ,medicine.medical_specialty ,Visible Light ,Adolescent ,Science ,Ocular Anatomy ,Young Adult ,Age groups ,Ocular System ,Age related ,Ophthalmology ,medicine ,Humans ,Ocular Physiological Phenomena ,Vision, Ocular ,Aged ,Color Vision ,business.industry ,Cognitive Psychology ,Color test ,Biology and Life Sciences ,Afferent Neurons ,Cell Biology ,Luminance ,Age Groups ,Cellular Neuroscience ,People and Places ,Cognitive Science ,Eyes ,Perception ,Population Groupings ,business ,Head ,Neuroscience - Abstract
Purpose To evaluate the age-related change in color visual acuity (CVA) in normal eyes. Methods In total, 162 normal eyes (162 subjects, women: 52, men: 110, age range: 15–68 years) with best-corrected visual acuity (BCVA) ≥20/13 were enrolled. Fifteen colors from the New Color Test (chroma 6) were applied to Landolt “C” rings, white point D65 was applied as background, and a luminance of 30 cd/m2 was set for both the rings and the background. These rings were used to measure the chromatic spatial discrimination acuity as the CVA value, while changing the stimulus size. Correlations of the CVA value of each color and age were evaluated. Mean CVA values of all 15 colors (logarithm of the minimum angle of resolution) were compared between age groups in 10-year increments. Results Nine CVA values (red, yellow-red, red-yellow, green, blue-green, green-blue, purple, red-purple, and purple-red) were negatively correlated with age (all pp Conclusions The CVA values related to the medium/long-wavelength-sensitive cones were more susceptible to aging than those related to the short-wavelength-sensitive cones. This differed from previous reports, and may be related to the difference in the range of foveal cone function evaluated with each examination.
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- 2021
8. Drosophila fabp is required for light-dependent Rhodopsin-1 clearance and photoreceptor survival
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Huai-Wei Huang and Hyung Don Ryoo
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Photoreceptors ,Retinal degeneration ,Cancer Research ,Sensory Receptors ,Eye Diseases ,Light ,genetic structures ,Mutant ,Social Sciences ,Organic chemistry ,QH426-470 ,Biochemistry ,chemistry.chemical_compound ,Medical Conditions ,RNA interference ,Animal Cells ,Medicine and Health Sciences ,Drosophila Proteins ,Psychology ,Vitamin A ,Genetics (clinical) ,Neurons ,biology ,Drosophila Melanogaster ,Physics ,Electromagnetic Radiation ,Retinal Degeneration ,Eukaryota ,Animal Models ,Vitamins ,Cell biology ,Insects ,Nucleic acids ,Physical sciences ,Chemistry ,Phenotype ,Experimental Organism Systems ,Genetic interference ,Rhodopsin ,Retinal Disorders ,Drosophila ,Photoreceptor Cells, Invertebrate ,Sensory Perception ,Epigenetics ,lipids (amino acids, peptides, and proteins) ,Cellular Types ,Anatomy ,Drosophila melanogaster ,Research Article ,Signal Transduction ,Arthropoda ,Protein degradation ,Research and Analysis Methods ,Retina ,Chemical compounds ,Model Organisms ,Ocular System ,Organic compounds ,medicine ,Genetics ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Endoplasmic reticulum ,Cognitive Psychology ,Organisms ,Biology and Life Sciences ,Afferent Neurons ,Retinal ,Cell Biology ,biology.organism_classification ,medicine.disease ,Invertebrates ,Ophthalmology ,Proteostasis ,chemistry ,Cellular Neuroscience ,Mutation ,Animal Studies ,biology.protein ,Cognitive Science ,Eyes ,RNA ,Perception ,Gene expression ,sense organs ,Transcriptome ,Zoology ,Entomology ,Head ,Neuroscience - Abstract
Rhodopsins are light-detecting proteins coupled with retinal chromophores essential for visual function. Coincidentally, dysfunctional Rhodopsin homeostasis underlies retinal degeneration in humans and model organisms. Drosophila ninaEG69D mutant is one such example, where the encoded Rh1 protein imposes endoplasmic reticulum (ER) stress and causes light-dependent retinal degeneration. The underlying reason for such light-dependency remains unknown. Here, we report that Drosophila fatty acid binding protein (fabp) is a gene induced in ninaEG69D/+ photoreceptors, and regulates light-dependent Rhodopsin-1 (Rh1) protein clearance and photoreceptor survival. Specifically, our photoreceptor-specific gene expression profiling study in ninaEG69D/+ flies revealed increased expression of fabp together with other genes that control light-dependent Rh1 protein degradation. fabp induction in ninaEG69D photoreceptors required vitamin A and its transporter genes. In flies reared under light, loss of fabp caused an accumulation of Rh1 proteins in cytoplasmic vesicles. The increase in Rh1 levels under these conditions was dependent on Arrestin2 that mediates feedback inhibition of light-activated Rh1. fabp mutants exhibited light-dependent retinal degeneration, a phenotype also found in other mutants that block light-induced Rh1 degradation. These observations reveal a previously unrecognized link between light-dependent Rh1 proteostasis and the ER-stress imposing ninaEG69D mutant that cause retinal degeneration., Author summary Rhodopsins are light-detecting proteins that use retinoids as chromophore co-factors. Rhodopsins are tighly regulated in photoreceptors, as dysfunctional Rhodopsins cause photoreceptor degeneration. The precise mechanisms by which photoreceptors regulate Rhodopsin homeostasis remains unclear. Here, we report that Drosophila fatty acid binding protein (fabp) is a gene required for Rhodopsin-1 (Rh1) protein homeostasis and photoreceptor survival. Specifically, we found that fabp is among the genes induced by an endoplasmic reticulum (ER) stress-imposing Rhodopsin-1 (Rh1) mutant, ninaEG69D, which serves as a Drosophila model for Retinitis Pigmentosa. We further found that fabp induction in ninaEG69D photoreceptors required vitamin A and its transporter genes. fabp was required in photoreceptors to help degrade light-activated Rh1. In the absence of fabp, Rh1 accumulated in cytoplasmic vesicles in a light-dependent manner, and exhibited light-dependent retinal degeneration. These observations indicate that fabp is required for light-induced Rh1 degradation and photoreceptor survival.
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- 2021
9. cGMP-phosphodiesterase inhibition prevents hypoxia-induced cell death activation in porcine retinal explants
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María Pilar Marín, Cristina Martinez-Fernandez de la Camara, Regina Rodrigo, Agustín Lahoz, José M. Millán, David Hervás, and Lorena Olivares-González
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Photoreceptors ,0301 basic medicine ,Retinal degeneration ,Sensory Receptors ,Pulmonology ,Phosphodiesterase Inhibitors ,Swine ,Social Sciences ,lcsh:Medicine ,Pharmacology ,Biochemistry ,Antioxidants ,Tissue Culture Techniques ,chemistry.chemical_compound ,0302 clinical medicine ,Superoxides ,Animal Cells ,Pyruvic Acid ,Medicine and Health Sciences ,Psychology ,Hypoxia ,lcsh:Science ,Cyclic GMP ,Neurons ,Multidisciplinary ,Cell Death ,biology ,Caspase 3 ,Retinal Degeneration ,Phosphodiesterase ,Oxides ,Chemistry ,medicine.anatomical_structure ,Cell Processes ,Physical Sciences ,Retinal Disorders ,Sensory Perception ,Anatomy ,Cellular Types ,Poly(ADP-ribose) Polymerases ,medicine.symptom ,Research Article ,Signal Transduction ,Ocular Anatomy ,Retina ,Superoxide dismutase ,03 medical and health sciences ,Ocular System ,Medical Hypoxia ,medicine ,Animals ,Lactic Acid ,Cyclic guanosine monophosphate ,Phosphoric Diester Hydrolases ,lcsh:R ,Chemical Compounds ,Biology and Life Sciences ,Afferent Neurons ,Retinal ,Cell Biology ,Hypoxia (medical) ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Ophthalmology ,Oxidative Stress ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Cellular Neuroscience ,biology.protein ,lcsh:Q ,Zaprinast ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP) has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE) with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O-2) for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation) mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities) and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions.
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- 2021
10. Oxytocin receptor disruption in Avil-expressing cells results in blunted sociability and increased inter-male aggression
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Ashley Moses, Manal Tabbaa, and Elizabeth A. D. Hammock
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Male ,Sensory Receptors ,Social Sciences ,Nervous System ,Mice ,Medicine and Health Sciences ,Psychology ,Nerve Tissue ,Mice, Knockout ,Mammals ,Multidisciplinary ,Animal Behavior ,Microfilament Proteins ,Neural crest ,Eukaryota ,Aggression ,medicine.anatomical_structure ,Neural Crest ,Receptors, Oxytocin ,Peripheral nervous system ,Animal Sociality ,Vertebrates ,Medicine ,Female ,Sensory Perception ,medicine.symptom ,Anatomy ,medicine.drug ,Research Article ,Signal Transduction ,Science ,Central nervous system ,Biology ,Rodents ,medicine ,Animals ,Social Behavior ,Behavior ,Neural tube ,Organisms ,Cognitive Psychology ,Biology and Life Sciences ,Cell Biology ,Oxytocin receptor ,Biological Tissue ,Oxytocin ,Gene Expression Regulation ,Amniotes ,Cognitive Science ,Perception ,Ganglia ,Neuroscience ,Zoology ,Social behavior - Abstract
Social behaviors are foundational to society and quality of life while social behavior extremes are core symptoms in a variety of psychopathologies and developmental disabilities. Oxytocin (OXT) is a neuroactive hormone that regulates social behaviors through its receptor (OXTR), with all previously identified social behavior effects attributed to the central nervous system, which has developmental origins in the neural tube. However, OXTR are also present in neural crest-derived tissue including sensory ganglia of the peripheral nervous system. Avil encodes for the actin-binding protein ADVILLIN, is expressed in neural crest-derived cells, and was therefore used as a target in this study to knock out OXTR expression in neural-crest derived cells. Here, we tested if OXTRs specifically expressed in Avil positive neural crest-derived cells are necessary for species-typical adult social behaviors using a Cre-LoxP strategy. Genetically modified male and female mice lacking OXTR in Avil expressing cells (OXTRAvil KO) were tested for sociability and preference for social novelty. Males were also tested for resident intruder aggression. OXTRAvil KO males and females had reduced sociability compared to OXTRAvil WT controls. Additionally, OXTRAvil KO males had increased aggressive behaviors compared to controls. These data indicate that OXTRs in cells of neural crest origin are important regulators of typical social behaviors in C57BL/6J adult male and female mice and point to needed directions of future research.
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- 2021
11. Identification of multiple odorant receptors essential for pyrethrum repellency in Drosophila melanogaster
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Rufus Isaacs, Peng Xu, Ke Dong, Yuzhe Du, Eugênio E. Oliveira, Kazuhiko Matsuda, Mengli Chen, Genki Takamatsu, Qiang Wang, Phil Duran, Makoto Ihara, Yoshiko Nomura, Lan Jiang, Yahui Liu, and Felipe Andreazza
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0301 basic medicine ,Cancer Research ,Insecticides ,Sensory Receptors ,Pyrethrum ,Social Sciences ,Insect ,QH426-470 ,Receptors, Odorant ,0302 clinical medicine ,Animal Cells ,Pyrethrins ,Melanogaster ,Psychology ,Drosophila Proteins ,Receptor ,Materials ,Genetics (clinical) ,media_common ,Neurons ,Chrysanthemum cinerariifolium ,biology ,Drosophila Melanogaster ,Eukaryota ,Agriculture ,Animal Models ,Insects ,Experimental Organism Systems ,Physical Sciences ,Olfactory Receptors ,Insect Pests ,Drosophila ,Sensory Perception ,Drosophila melanogaster ,Cellular Types ,Insect repellent ,Sesquiterpenes ,Research Article ,Signal Transduction ,animal structures ,Arthropoda ,media_common.quotation_subject ,Materials Science ,Flowers ,Research and Analysis Methods ,Olfactory Receptor Neurons ,03 medical and health sciences ,Pests ,Model Organisms ,Botany ,Genetics ,Animals ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,fungi ,Organisms ,Cognitive Psychology ,Biology and Life Sciences ,Afferent Neurons ,Cell Biology ,biology.organism_classification ,Invertebrates ,030104 developmental biology ,Cellular Neuroscience ,Insect Repellents ,Odorants ,Animal Studies ,Cognitive Science ,Perception ,Zoology ,Entomology ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Pyrethrum extract from dry flowers of Tanacetum cinerariifolium (formally Chrysanthemum cinerariifolium) has been used globally as a popular insect repellent against arthropod pests for thousands of years. However, the mechanistic basis of pyrethrum repellency remains unknown. In this study, we found that pyrethrum spatially repels and activates olfactory responses in Drosophila melanogaster, a genetically tractable model insect, and the closely-related D. suzukii which is a serious invasive fruit crop pest. The discovery of spatial pyrethrum repellency and olfactory response to pyrethrum in D. melanogaster facilitated our identification of four odorant receptors, Or7a, Or42b, Or59b and Or98a that are responsive to pyrethrum. Further analysis showed that the first three Ors are activated by pyrethrins, the major insecticidal components in pyrethrum, whereas Or98a is activated by (E)-β-farnesene (EBF), a sesquiterpene and a minor component in pyrethrum. Importantly, knockout of Or7a, Or59b or Or98a individually abolished fly avoidance to pyrethrum, while knockout of Or42b had no effect, demonstrating that simultaneous activation of Or7a, Or59b and Or98a is required for pyrethrum repellency in D. melanogaster. Our study provides insights into the molecular basis of repellency of one of the most ancient and globally used insect repellents. Identification of pyrethrum-responsive Ors opens the door to develop new synthetic insect repellent mixtures that are highly effective and broad-spectrum., Author summary Pyrethrum extract began to be used as an insect repellent against biting arthropods and blood-sucking mosquitoes since ancient times. However, the mechanisms underlying pyrethrum repellency remains unknown. In this study, we took advantage of Drosophila melanogaster as a model insect system for olfaction studies and conducted a series of electrophysiological, molecular genetic and behavioral experiments to understand the mechanism of pyrethrum repellency in D. melanogaster. We discovered that pyrethrum repels D. melanogaster by activating multiple odorant receptors (Ors). Apparently simultaneous activation of these Ors by various components in pyrethrum extract makes pyrethrum one of the most potent and the longest used insect repellents in the human history.
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- 2021
12. Modelling the visual world of a velvet worm
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Mikael Ljungholm and Dan-Eric Nilsson
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Photoreceptors ,Visual acuity ,Sensory Receptors ,genetic structures ,Computer science ,Vision ,Visual Acuity ,Social Sciences ,Cornea ,Animal Cells ,Medicine and Health Sciences ,Psychology ,Computer vision ,Photopigment ,Biology (General) ,Neurons ,Eye Lens ,Animal Behavior ,Orientation (computer vision) ,3D reconstruction ,Image plane ,Optical Lenses ,Visual field ,medicine.anatomical_structure ,Optical Equipment ,Lens (anatomy) ,Engineering and Technology ,Ray tracing (graphics) ,Sensory Perception ,medicine.symptom ,Anatomy ,Cellular Types ,Research Article ,Signal Transduction ,QH301-705.5 ,Ocular Anatomy ,Equipment ,Retina ,Ocular System ,medicine ,Animals ,Behavior ,business.industry ,Cognitive Psychology ,Biology and Life Sciences ,Afferent Neurons ,Computational Biology ,Cell Biology ,Invertebrates ,eye diseases ,Cellular Neuroscience ,Eyes ,Cognitive Science ,Perception ,Artificial intelligence ,sense organs ,Visual Fields ,business ,Head ,Zoology ,Neuroscience - Abstract
In many animal phyla, eyes are small and provide only low-resolution vision for general orientation in the environment. Because these primitive eyes rarely have a defined image plane, traditional visual-optics principles cannot be applied. To assess the functional capacity of such eyes we have developed modelling principles based on ray tracing in 3D reconstructions of eye morphology, where refraction on the way to the photoreceptors and absorption in the photopigment are calculated incrementally for ray bundles from all angles within the visual field. From the ray tracing, we calculate the complete angular acceptance function of each photoreceptor in the eye, revealing the visual acuity for all parts of the visual field. We then use this information to generate visual filters that can be applied to high resolution images or videos to convert them to accurate representations of the spatial information seen by the animal. The method is here applied to the 0.1 mm eyes of the velvet worm Euperipatoides rowelli (Onychophora). These eyes of these terrestrial invertebrates consist of a curved cornea covering an irregular but optically homogeneous lens directly joining a retina packed with photoreceptive rhabdoms. 3D reconstruction from histological sections revealed an asymmetric eye, where the retina is deeper in the forward-pointing direction. The calculated visual acuity also reveals performance differences across the visual field, with a maximum acuity of about 0.11 cycles/deg in the forward direction despite laterally pointing eyes. The results agree with previous behavioural measurements of visual acuity, and suggest that velvet worm vision is adequate for orientation and positioning within the habitat., Author summary It is difficult to understand the roles that vision may have in animals with visual performance very different to our own. Many invertebrates such as flatworms, polychaetes, onychophorans, gastropod molluscs and numerous arthropods have tiny eyes with unknown visual abilities. At best, behavioural experiments can reveal visual performance limits for specific behaviours but they will not give general information about what is visible to the animal, which is crucial for understanding the roles vision may have. Here we use ray tracing applied to accurate anatomical/optical models of the eyes of a velvet worm to reconstruct the visual acuity in all parts of the visual field. We also use the calculated visual performance to closely simulate what animals would see in their natural habitat. The method can be applied to any (preferably small) eye and offers an alternative strategy that may yield information about the visual capacity that is otherwise hard to obtain.
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- 2021
13. From musk to body odor: Decoding olfaction through genetic variation
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Li, Bingjie, Kamarck, Marissa L, Peng, Qianqian, Lim, Fei-Ling, Keller, Andreas, Smeets, Monique A M, Mainland, Joel D, Wang, Sijia, Leerstoel Smeets, Social-cognitive and interpersonal determinants of behaviour, Leerstoel Smeets, and Social-cognitive and interpersonal determinants of behaviour
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Male ,Body Odor ,Cancer Research ,Sensory Receptors ,Heredity ,Single Nucleotide Polymorphisms ,Social Sciences ,QH426-470 ,Receptors, Odorant ,Psychology ,Genetics(clinical) ,Genetics (clinical) ,Ecology ,Organic Compounds ,Middle Aged ,Smell ,Genetic Mapping ,Chemistry ,Physical Sciences ,Olfactory Receptors ,Female ,Sensory Perception ,psychological phenomena and processes ,Research Article ,Signal Transduction ,Adult ,Adolescent ,Evolution ,Polymorphism, Single Nucleotide ,Young Adult ,Asian People ,Behavior and Systematics ,Genetics ,Humans ,Benzopyrans ,Caproates ,Molecular Biology ,Alleles ,Ecology, Evolution, Behavior and Systematics ,Evolutionary Biology ,Aldehydes ,Population Biology ,Organic Chemistry ,Cognitive Psychology ,Chemical Compounds ,Reproducibility of Results ,Biology and Life Sciences ,Cell Biology ,Olfactory Perception ,Haplotypes ,Genetic Loci ,Genetic Polymorphism ,Cognitive Science ,Perception ,Population Genetics ,Neuroscience - Abstract
The olfactory system combines input from multiple receptor types to represent odor information, but there are few explicit examples relating olfactory receptor (OR) activity patterns to odor perception. To uncover these relationships, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1000 Han Chinese and validated results for six of these odors in an ethnically diverse population (n = 364). In both populations, consistent with previous studies, we replicated three previously reported associations (β-ionone/OR5A1, androstenone/OR7D4, cis-3-hexen-1-ol/OR2J3 LD-band), but not for odors containing aldehydes, suggesting that olfactory phenotype/genotype studies are robust across populations. Two novel associations between an OR and odor perception contribute to our understanding of olfactory coding. First, we found a SNP in OR51B2 that associated with trans-3-methyl-2-hexenoic acid, a key component of human underarm odor. Second, we found two linked SNPs associated with the musk Galaxolide in a novel musk receptor, OR4D6, which is also the first human OR shown to drive specific anosmia to a musk compound. We noticed that SNPs detected for odor intensity were enriched with amino acid substitutions, implying functional changes of odor receptors. Furthermore, we also found that the derived alleles of the SNPs tend to be associated with reduced odor intensity, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study provides information about coding for human body odor, and gives us insight into broader mechanisms of olfactory coding, such as how differential OR activation can converge on a similar percept., Author summary Although genetic diversity in the olfactory receptor repertoire contributes to variation in odor perception, we have few explicit predictions relating variation in a specific OR to perception. Here, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1000 Han Chinese and validated results for six of these odors in an ethnically diverse population (n = 364). We identified novel receptors for musk and human body odor that have implications for how structurally different molecules can have similar odors. Summarizing all the published genetic variation that associates with odor perception, we found that individuals with ancestral versions of the receptors tend to rate the corresponding odor as more intense, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study of olfactory genetic and perceptual variation will improve our understanding of how the olfactory system encodes odor properties.
- Published
- 2022
14. Transcriptome sequencing revealed the influence of blue light on the expression levels of light-stress response genes in Centella asiatica
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Yanisa Ketngamkum, Wanapinun Nawae, Atchara Paemanee, Sithichoke Tangphatsornruang, Wirulda Pootakham, Thippawan Yoocha, Theerayut Toojinda, Kanokwan Romyanon, and Nattapol Narong
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Photoreceptors ,Sensory Receptors ,Light ,Photosystem II ,Molecular biology ,Flavonoid ,Gene Expression ,Social Sciences ,Biochemistry ,Sequencing techniques ,Animal Cells ,Gene Expression Regulation, Plant ,Gene expression ,Psychology ,Neurons ,chemistry.chemical_classification ,Multidisciplinary ,Centella ,Physics ,Electromagnetic Radiation ,Gene Ontologies ,RNA sequencing ,Genomics ,Cell biology ,Physical Sciences ,Medicine ,Sensory Perception ,Cellular Types ,Research Article ,Signal Transduction ,Visible Light ,Science ,Biology ,Biosynthesis ,Genes, Plant ,Stress, Physiological ,DNA-binding proteins ,Genetics ,Gene Regulation ,White Light ,Gene ,Transcription factor ,Cognitive Psychology ,Biology and Life Sciences ,Proteins ,Afferent Neurons ,Computational Biology ,RNA ,Cell Biology ,Genome Analysis ,biology.organism_classification ,Regulatory Proteins ,Research and analysis methods ,Molecular biology techniques ,chemistry ,Cellular Neuroscience ,Xanthophyll ,Cognitive Science ,Perception ,Transcriptome ,Transcription Factors ,Neuroscience - Abstract
Centella asiatica is rich in medical and cosmetic properties. While physiological responses of C. asiatica to light have been widely reported, the knowledge of the effects of light on its gene expression is sparse. In this study, we used RNA sequencing (RNA-seq) to investigate the expression of the C. asiatica genes in response to monochromatic red and blue light. Most of the differentially expressed genes (DEGs) under blue light were up-regulated but those under red light were down-regulated. The DEGs encoded for CRY-DASH and UVR3 were among up-regulated genes that play significant roles in responses under blue light. The DEGs involved in the response to photosystem II photodamages and in the biosynthesis of photoprotective xanthophylls were also up-regulated. The expression of flavonoid biosynthetic DEGs under blue light was up-regulated but that under red light was down-regulated. Correspondingly, total flavonoid content under blue light was higher than that under red light. The ABI5, MYB4, and HYH transcription factors appeared as hub nodes in the protein-protein interaction network of the DEGs under blue light while ERF38 was a hub node among the DEGs under red light. In summary, stress-responsive genes were predominantly up-regulated under blue light to respond to stresses that could be induced under high energy light. The information obtained from this study can be useful to better understand the responses of C. asiatica to different light qualities.
- Published
- 2021
15. Analysis of growth cone extension in standardized coordinates highlights self-organization rules during wiring of the Drosophila visual system
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Lani F. Wu, Weiyue Ji, Steven J. Altschuler, and Perrimon, Norbert
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Photoreceptors ,Cancer Research ,Sensory Receptors ,Vision ,Coordinate system ,Social Sciences ,QH426-470 ,Nervous System ,Frame of reference ,Animal Cells ,Neural Pathways ,Medicine and Health Sciences ,Psychology ,Drosophila Proteins ,Invertebrate ,Genetics (clinical) ,Electronic circuit ,Neurons ,Drosophila Melanogaster ,Eukaryota ,Animal Models ,Extension (predicate logic) ,Insects ,Experimental Organism Systems ,Cell Processes ,Photoreceptor Cells, Invertebrate ,Sensory Perception ,Drosophila ,Cellular Types ,Anatomy ,Research Article ,Signal Transduction ,Biotechnology ,Arthropoda ,Growth Cones ,Biology ,Research and Analysis Methods ,Topology ,Cell Growth ,Superposition principle ,Model Organisms ,Developmental Neuroscience ,Ocular ,Genetics ,Animals ,Photoreceptor Cells ,Growth cone ,Immunohistochemistry Techniques ,Eye Disease and Disorders of Vision ,Molecular Biology ,Vision, Ocular ,Ecology, Evolution, Behavior and Systematics ,Self-organization ,Cognitive Psychology ,Organisms ,Neurosciences ,Biology and Life Sciences ,Afferent Neurons ,Cell Biology ,Invertebrates ,Histochemistry and Cytochemistry Techniques ,Neuroanatomy ,Cellular Neuroscience ,Immunologic Techniques ,Animal Studies ,Cognitive Science ,Perception ,Neural Circuit Formation ,sense organs ,Zoology ,Entomology ,Neuroscience ,Developmental Biology - Abstract
A fascinating question in neuroscience is how ensembles of neurons, originating from different locations, extend to the proper place and by the right time to create precise circuits. Here, we investigate this question in the Drosophila visual system, where photoreceptors re-sort in the lamina to form the crystalline-like neural superposition circuit. The repeated nature of this circuit allowed us to establish a data-driven, standardized coordinate system for quantitative comparison of sparsely perturbed growth cones within and across specimens. Using this common frame of reference, we investigated the extension of the R3 and R4 photoreceptors, which is the only pair of symmetrically arranged photoreceptors with asymmetric target choices. Specifically, we found that extension speeds of the R3 and R4 growth cones are inherent to their cell identities. The ability to parameterize local regularity in tissue organization facilitated the characterization of ensemble cellular behaviors and dissection of mechanisms governing neural circuit formation., Author summary One of the most fascinating questions in neuroscience is how complex neural circuits form. Here, we investigate self-organization principles during neuronal development in the visual circuit of fruit flies. We utilized the regularity of the tissue environment to establish a developmental coordinate system during wiring, which allowed us to uncover a role for cell identity in governing neuronal growth cone extension speed. Our study highlights the importance of velocity control in the precise formation of complex neuronal circuits, as well as the use of developmental coordinates in identifying ensemble behaviors of tissue patterning.
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- 2021
16. Phototransduction in retinal cones: Analysis of parameter importance
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Vsevolod V. Gurevich, Emmanuele DiBenedetto, Heidi E. Hamm, Clint L. Makino, Giovanni Caruso, and Colin Klaus
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Photoreceptors ,Sensory Receptors ,Light ,Statistical methods ,genetic structures ,Vision ,Mass diffusivity ,Social Sciences ,Mice ,Animal Cells ,Psychology ,Cyclic GMP ,Mice, Knockout ,Neurons ,Mass Diffusivity ,Multidisciplinary ,biology ,Chemistry ,Hydrolysis ,Physics ,Statistics ,Chemical Reactions ,Eukaryota ,Sobol sequence ,Animal Models ,Retinal Cones ,Monte Carlo method ,medicine.anatomical_structure ,Experimental Organism Systems ,Osteichthyes ,Rhodopsin ,Physical Sciences ,Vertebrates ,Retinal Cone Photoreceptor Cells ,Medicine ,Sensory Perception ,Transducin ,Cellular Types ,Biological system ,Research Article ,Signal Transduction ,Visual phototransduction ,Light Signal Transduction ,Carps ,Markov Models ,Science ,Systems biology ,Mouse Models ,Research and Analysis Methods ,Model Organisms ,medicine ,Animals ,Vision, Ocular ,Retina ,Chemical Physics ,Cognitive Psychology ,Organisms ,Biology and Life Sciences ,Afferent Neurons ,Cell Biology ,Probability Theory ,Fish ,Cellular Neuroscience ,Phototransduction ,Animal Studies ,biology.protein ,Cognitive Science ,Mathematical and statistical techniques ,Perception ,sense organs ,Zoology ,Mathematics ,Neuroscience - Abstract
In daylight, cone photoreceptors in the retina are responsible for the bulk of visual perception, yet compared to rods, far less is known quantitatively about their biochemistry. This is partly because it is hard to isolate and purify cone proteins. The issue is also complicated by the synergistic interaction of these parameters in producing systems biology outputs, such as photoresponse. Using a 3-D resolved, finite element model of cone outer segments, here we conducted a study of parameter significance using global sensitivity analysis, by Sobol indices, which was contextualized within the uncertainty surrounding these parameters in the available literature. The analysis showed that a subset of the parameters influencing the circulating dark current, such as the turnover rate of cGMP in the dark, may be most influential for variance with experimental flash response, while the shut-off rates of photoexcited rhodopsin and phosphodiesterase also exerted sizable effect. The activation rate of transducin by rhodopsin and the light-induced hydrolysis rate of cGMP exerted measurable effects as well but were estimated as relatively less significant. The results of this study depend on experimental ranges currently described in the literature and should be revised as these become better established. To that end, these findings may be used to prioritize parameters for measurement in future investigations.
- Published
- 2021
17. Mechanosensing uses the intricate internal organization of bacteria to regulate surface behaviors
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Patino, Ramiro
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- Microbiology, Acinetobacter species, mechanosensing, Pseudomonas aeruginosa, sensory adaptation, sensory system, signal transduction
- Abstract
Bacteria use conserved signal transduction pathways, called sensory systems, to sense environmental stimuli. Most of our understanding of sensory systems in bacteria, however, comes from the chemotaxis system of Escherichia coli, which senses chemical gradients to control the direction of flagellar-based motility (chemosensing). Importantly, bacteria can also sense mechanical stimuli to actively shape their physiology. An in-depth mechanistic understanding of mechanosensory systems, when compared to their chemosensory counterparts, is however lacking. This dissertation presents work towards understanding mechanosensing in the important opportunistic human pathogen Pseudomonas aeruginosa. This Gram-negative bacterium uses Type IV pili (TFP), retractile polarly localized appendages, to sense mechanical forces generated during surface contact at one cell pole. We and others have demonstrated that spatially resolved mechanical stimuli transmitted by TFP activates the Pil-Chp mechanosensory system. Upon surface contact, TFP transmits mechanical stimuli to the Pil-Chp receptor, PilJ, thereby altering the autophosphorylation state of ChpA and thus the phosphorylation of PilG and PilH, the antagonistic Pil-Chp response regulators. PilG and PilH inversely control two outputs of the Pil-Chp system in P. aeruginosa: cAMP production and twitching motility. Sensing of surface contact by the Pil-Chp system activates the membrane bound CyaB adenylate cyclase, which catalyzes the production of the second messenger, cyclic adenosine monophosphate (cAMP). cAMP binds to the Vfr transcription factor, leading to altered transcription of >200 genes involved in acute virulence as well as selected TFP regulatory proteins. Signal processing through PilG and PilH is critical for surface-dependent cAMP production. PilG promotes cAMP production and upregulation of the surface dependent transcriptional program while PilH has the opposite effect. The Pil-Chp mechanosensory system is required for twitching motility, partially independently of cAMP levels. In Chapter 2, we demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from TFP, in a process called mechanotaxis. The Pil-Chp system controls the balance of forward and reverse twitching motility of single cells in response to the mechanical inputs. We show that the Pil-Chp response regulators PilG and PilH control the polarization of the TFP extension motor PilB. PilG localizes to both poles, but shows greater accumulation at the leading pole, where it stimulates polarization favoring forward migration. In contrast, PilH, is primarily cytoplasmic, thereby globally antagonizing PilG. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localization of response regulators establishes a signaling landscape known as local-excitation, global-inhibition in higher order organisms.In Chapter 3, we demonstrate that PilG and PilH enable dynamic cell polarization by coupling their antagonistic functions on TFP extension. By precisely quantifying the localization of fluorescent protein fusions, we show that phosphorylation of PilG by the histidine kinase ChpA controls PilG polarization. Although PilH is not inherently required for twitching reversals, upon phosphorylation, PilH becomes activated and breaks the local positive feedback established by PilG so that forward-twitching cells can reverse. To spatially resolve mechanical signals, the Pil-Chp system thus locally transduces signals with a main output response regulator, PilG. To respond to signal changes, Chp uses its second regulator, PilH, to break the local feedback. In Chapter 4, we report the mechanism of sensory adaptation in the Pil-Chp mechanosensory system. Bacterial sensory adaptation has primarily been studied in flagellar-mediated chemotaxis, where reversible methylation of sensory receptors by a methyltransferase and a methylesterase “tune” their sensitivity of signaling. The Pil-Chp system encodes the PilK methyltransferase, predicted to methylate PilJ, and the ChpB methylesterase, predicted to demethylate PilJ; however, whether sensory adaptation occurs in response to surface contact remained underexplored. Using biochemistry, genetics, and cell biology, we discovered that PilK and ChpB are segregated to opposing cell poles as P. aeruginosa explore surfaces. By coordinating the localization of both enzymes, we found that the Pil-Chp response regulators influence local PilJ methylation in vivo. We propose a model in which spatially resolved mechanical inputs transmitted by TFP not only alter PilG and PilH signaling mechanisms but locally controls PilJ methylation to modulate twitching motility reversal rates and surface-dependent cAMP production. Despite decades of chemosensory adaptation studies, our work has uncovered an unrecognized mechanism that bacteria use to achieve adaptation to mechanical sensory stimuli.Acinetobacter species are opportunistic pathogens that are ubiquitous throughout the environment and are emerging as a public health threat around the world due to their widespread multidrug resistance. Intriguingly, many Acinetobacter strains encode homologs of the P. aeruginosa Pil-Chp mechanosensory system. In Chapter 5, we demonstrate that A. nosocomialis strain M2, a pathogenic member of the Acinetobacter calcoaceticus-baumannii complex, has a robust surface-dependent transcriptional response. We speculate that the homologous Pil-Chp mechanosensory system is responsible for the surface-dependent transcriptional response that we report in this dissertation. Overall, this dissertation demonstrates that mechanosensing through the Pil-Chp system takes advantage of the intricate internal organization of bacteria to sense spatially resolved mechanical information. As medically Acinetobacter species exhibit a surface transcriptional response, defining the mechanosensing mechanism of Acinetobacter species represents an exciting area of investigation. Understanding the mechanisms of bacterial mechanosensing may lead to the generation of desperately needed therapeutics to treat multi-drug resistant infections, such as the ones typically caused by P. aeruginosa and medically relevant Acinetobacter species.
- Published
- 2024
18. Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics.
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Genovese, Federica, Reisert, Johannes, and Kefalov, Vladimir J.
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SENSORY neurons ,PHOTORECEPTORS ,GENETIC transduction ,SMELL ,CELLULAR signal transduction - Abstract
The past decades have seen tremendous progress in our understanding of the function of photoreceptors and olfactory sensory neurons, uncovering the mechanisms that determine their properties and, ultimately, our ability to see and smell. This progress has been driven to a large degree by the powerful combination of physiological experimental tools and genetic manipulations, which has enabled us to identify the main molecular players in the transduction cascades of these sensory neurons, how their properties affect the detection and discrimination of stimuli, and how diseases affect our senses of vision and smell. This review summarizes some of the common and unique features of photoreceptors and olfactory sensory neurons that make these cells so exciting to study. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
19. Regulation of gene expression by non-phosphorylated response regulators
- Author
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Gomez-Arrebola, Carmen, Solano, Cristina, and Lasa, Iñigo
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- 2021
- Full Text
- View/download PDF
20. Multistep Signaling in Nature: A Close-Up of Geobacter Chemotaxis Sensing.
- Author
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Silva, Marta A. and Salgueiro, Carlos A.
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GEOBACTER ,GEOBACTER sulfurreducens ,CELLULAR signal transduction ,REDUCTION potential ,PHOSPHORYLATION ,CHEMOTAXIS - Abstract
Environmental changes trigger the continuous adaptation of bacteria to ensure their survival. This is possible through a variety of signal transduction pathways involving chemoreceptors known as methyl-accepting chemotaxis proteins (MCP) that allow the microorganisms to redirect their mobility towards favorable environments. MCP are two-component regulatory (or signal transduction) systems (TCS) formed by a sensor and a response regulator domain. These domains synchronize transient protein phosphorylation and dephosphorylation events to convert the stimuli into an appropriate cellular response. In this review, the variability of TCS domains and the most common signaling mechanisms are highlighted. This is followed by the description of the overall cellular topology, classification and mechanisms of MCP. Finally, the structural and functional properties of a new family of MCP found in Geobacter sulfurreducens are revisited. This bacterium has a diverse repertoire of chemosensory systems, which represents a striking example of a survival mechanism in challenging environments. Two G. sulfurreducens MCP—GSU0582 and GSU0935—are members of a new family of chemotaxis sensor proteins containing a periplasmic PAS-like sensor domain with a c-type heme. Interestingly, the cellular location of this domain opens new routes to the understanding of the redox potential sensing signaling transduction pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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