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The UBR-1 ubiquitin ligase regulates glutamate metabolism to generate coordinated motor pattern in Caenorhabditis elegans
- Source :
- PLoS Genetics, Vol 14, Iss 4, p e1007303 (2018), PLoS Genetics
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- UBR1 is an E3 ubiquitin ligase best known for its ability to target protein degradation by the N-end rule. The physiological functions of UBR family proteins, however, remain not fully understood. We found that the functional loss of C. elegans UBR-1 leads to a specific motor deficit: when adult animals generate reversal movements, A-class motor neurons exhibit synchronized activation, preventing body bending. This motor deficit is rescued by removing GOT-1, a transaminase that converts aspartate to glutamate. Both UBR-1 and GOT-1 are expressed and critically required in premotor interneurons of the reversal motor circuit to regulate the motor pattern. ubr-1 and got-1 mutants exhibit elevated and decreased glutamate level, respectively. These results raise an intriguing possibility that UBR proteins regulate glutamate metabolism, which is critical for neuronal development and signaling.<br />Author summary Ubiquitin-mediated protein degradation is central to diverse biological processes. The selection of substrates for degradation is carried out by the E3 ubiquitin ligases, which target specific groups of proteins for ubiquitination. The human genome encodes hundreds of E3 ligases; many exhibit sequence conservation across animal species, including one such ligase called UBR1. Patients carrying mutations in UBR1 exhibit severe systemic defects, but the biology behinds UBR1’s physiological function remains elusive. Here we found that the C. elegans UBR-1 regulates glutamate level. When UBR-1 is defective, C. elegans exhibits increased glutamate; this leads to synchronization of motor neuron activity, hence defective locomotion when animals reach adulthood. UBR1-mediated glutamate metabolism may contribute to the physiological defects of UBR1 mutations.
- Subjects :
- 0301 basic medicine
Cancer Research
Nematoda
Enzyme Metabolism
Mutant
Protein metabolism
Biochemistry
chemistry.chemical_compound
Animal Cells
Enzyme Chemistry
Genetics (clinical)
Caenorhabditis elegans
Protein Metabolism
Neurons
Motor Neurons
biology
Glutamate receptor
Eukaryota
Neurochemistry
Neurotransmitters
Animal Models
Ubiquitin ligase
Cell biology
Experimental Organism Systems
Target protein
Glutamate
Cellular Types
Research Article
lcsh:QH426-470
Movement
Ubiquitin-Protein Ligases
Motor Proteins
Glutamic Acid
Research and Analysis Methods
Motor protein
03 medical and health sciences
Model Organisms
Interneurons
Molecular Motors
Genetics
Animals
Caenorhabditis elegans Proteins
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Organisms
Biology and Life Sciences
Proteins
Cell Biology
biology.organism_classification
Invertebrates
lcsh:Genetics
Metabolism
030104 developmental biology
chemistry
Cellular Neuroscience
Caenorhabditis
Enzymology
biology.protein
Motor Deficit
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 14
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....d9cdd32f9c0d567e554701e0ed954fba