RGD Reference Report - Membrane glycoprotein M6a interacts with the micro-opioid receptor and facilitates receptor endocytosis and recycling. - Rat Genome Database

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Membrane glycoprotein M6a interacts with the micro-opioid receptor and facilitates receptor endocytosis and recycling.

Authors: Wu, DF  Koch, T  Liang, YJ  Stumm, R  Schulz, S  Schroder, H  Hollt, V 
Citation: Wu DF, etal., J Biol Chem. 2007 Jul 27;282(30):22239-47. Epub 2007 Jun 4.
RGD ID: 8554757
Pubmed: PMID:17548356   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M700941200   (Journal Full-text)

Using a yeast two-hybrid screen, the neuronal membrane glycoprotein M6a, a member of the proteolipid protein family, was identified to be associated with the mu-opioid receptor (MOPr). Bioluminescence resonance energy transfer and co-immunoprecipitation experiments confirmed that M6a interacts agonist-independently with MOPr in human embryonic kidney 293 cells co-expressing MOPr and M6a. Co-expression of MOPr with M6a, but not with M6b or DM20, exists in many brain regions, further supporting a specific interaction between MOPr and M6a. After opioid treatment M6a co-internalizes and then co-recycles with MOPr to cell surface in transfected human embryonic kidney 293 cells. Moreover, the interaction of M6a and MOPr augments constitutive and agonist-dependent internalization as well as the recycling rate of mu-opioid receptors. On the other hand, overexpression of a M6a-negative mutant prevents mu-opioid receptor endocytosis, demonstrating an essential role of M6a in receptor internalization. In addition, we demonstrated the interaction of M6a with a number of other G protein-coupled receptors (GPCRs) such as the delta-opioid receptor, cannabinoid receptor CB1, and somatostatin receptor sst2A, suggesting that M6a might play a general role in the regulation of certain GPCRs. Taken together, these data provide evidence that M6a may act as a scaffolding molecule in the regulation of GPCR endocytosis and intracellular trafficking.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P335358554757PMID:17548356IntAct 
protein binding enablesIPIUniProtKB:Q812E98554757PMID:17548356IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Gpm6a  (glycoprotein m6a)
Oprm1  (opioid receptor, mu 1)


Additional Information