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Melanopsin Carboxy-terminus phosphorylation plasticity and bulk negative charge, not strict site specificity, achieves phototransduction deactivation
- Source :
- PLoS ONE, Vol 15, Iss 4, p e0228121 (2020), PLoS ONE
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- Melanopsin is a visual pigment expressed in a small subset of ganglion cells in the mammalian retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) and is implicated in regulating non-image forming functions such as circadian photoentrainment and pupil constriction and contrast sensitivity in image formation. Mouse melanopsin's Carboxy-terminus (C-terminus) possesses 38 serine and threonine residues, which can potentially serve as phosphorylation sites for a G-protein Receptor Kinase (GRK) and be involved in the deactivation of signal transduction. Previous studies suggest that S388, T389, S391, S392, S394, S395 on the proximal region of the C-terminus of mouse melanopsin are necessary for melanopsin deactivation. We expressed a series of mouse melanopsin C-terminal mutants in HEK293 cells and using calcium imaging, and we found that the necessary cluster of six serine and threonine residues, while being critical, are insufficient for proper melanopsin deactivation. Interestingly, the additional six serine and threonine residues adjacent to the required six sites, in either proximal or distal direction, are capable of restoring wild-type deactivation of melanopsin. These findings suggest an element of plasticity in the molecular basis of melanopsin phosphorylation and deactivation. In addition, C-terminal chimeric mutants and molecular modeling studies support the idea that the initial steps of deactivation and β-arrestin binding are centered around these critical phosphorylation sites (S388-S395). The degree of functional versatility described in this study, along with ipRGC biophysical heterogeneity and the possible use of multiple signal transduction cascades, might contribute to the diverse ipRGC light responses for use in non-image and image forming behaviors, even though all six sub types of ipRGCs express the same melanopsin gene OPN4.
- Subjects :
- 0301 basic medicine
Threonine
Models, Molecular
Light
Biochemistry
Serine
0302 clinical medicine
Cell Signaling
Post-Translational Modification
Phosphorylation
Amino Acids
0303 health sciences
Multidisciplinary
Organic Compounds
Chemistry
Physics
Electromagnetic Radiation
Calcium Imaging
Cell biology
beta-Arrestin 1
Physical Sciences
Amino Acid Analysis
Medicine
Signal transduction
Research Article
Signal Transduction
Protein Binding
Visual phototransduction
Melanopsin
Light Signal Transduction
Imaging Techniques
Recombinant Fusion Proteins
Science
Neuroimaging
Research and Analysis Methods
Transfection
Receptor, Angiotensin, Type 1
03 medical and health sciences
Calcium imaging
Hydroxyl Amino Acids
Humans
Calcium Signaling
Molecular Biology Techniques
Molecular Biology
030304 developmental biology
Molecular Biology Assays and Analysis Techniques
Organic Chemistry
HEK 293 cells
Intrinsically photosensitive retinal ganglion cells
Chemical Compounds
Rod Opsins
Biology and Life Sciences
Proteins
Cell Biology
030104 developmental biology
HEK293 Cells
Mutation
Mutagenesis, Site-Directed
Receptors, Adrenergic, beta-2
sense organs
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 15
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....5af3c601b619ebeea3c6b0f98614642f