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SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b
- Source :
- Biochemical Journal. 435:365-371
- Publication Year :
- 2011
- Publisher :
- Portland Press Ltd., 2011.
-
Abstract
- The central nervous system regulates neuronal excitability by macromolecular signalling complexes that consist of functionally related proteins, including neurotransmitter receptors, enzymes and scaffolds. The composition of these signal complexes is regulated by post-translational modifications, such as phosphorylation and SUMOylation (SUMO is small ubiquitin-related modifier). In the present study, we searched for proteins interacting with the intracellular C-termini of the metabotropic glutamate receptors mGluR8a and mGluR8b and identified proteins of the SUMOylation and NEDDylation machinery. The SUMO E3 ligases Pias1 [Pias is protein inhibitor of activated STAT (signal transducer and activator of transcription)] and Pias3L interacted strongly with mGluR8b, and were co-localized with the E2-conjugating Ubc9, SUMO1 and mGluR8b in cell bodies present in the ganglion cell layer of the mammalian retina. SUMO1 conjugation of Lys882, present in a bona fide consensus sequence for SUMOylation (VKSE) in the mGluR8b C-terminus, was enhanced by addition of Pias1, consistent with an interaction between both proteins. Mutation of Lys882 to arginine reduced, but did not abolish, mGluR8b SUMOylation. Co-mutating a second lysine residue (Lys903) located in the mGluR8b isoform-specific C-terminus largely prevented SUMO1 conjugation by Ubc9. Modelling studies suggested that Lys903 contacts Ubc9 and thus is part of the non-canonical SUMOylation site VKSG. In summary, the results of the present study show in vivo SUMOylation of the complete mGluR8b and co-localize proteins of the SUMOylation machinery in the retina.
- Subjects :
- Models, Molecular
Ubiquitin-Protein Ligases
Molecular Sequence Data
SUMO-1 Protein
SUMO protein
SUMO enzymes
Biology
Receptors, Metabotropic Glutamate
Models, Biological
Biochemistry
Gene Expression Regulation, Enzymologic
Retina
Mice
Neurotransmitter receptor
Catalytic Domain
Animals
Humans
Protein Isoforms
Protein Interaction Domains and Motifs
Protein inhibitor of activated STAT
Amino Acid Sequence
Protein Structure, Quaternary
Molecular Biology
Cells, Cultured
Sumoylation
Cell Biology
Protein Inhibitors of Activated STAT
Rats
Metabotropic glutamate receptor
STAT protein
Phosphorylation
Neddylation
Protein Processing, Post-Translational
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 435
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....8279a1ea52bb3d85f6beee36c4497fdd