Details

Autor(en) / Beteiligte

• Wu, Dai-Fei
• Koch, Thomas
• Liang, Ying-Jian
• Stumm, Ralf
• Schulz, Stefan
• Schröder, Helmut
• Höllt, Volker

Titel

Membrane Glycoprotein M6a Interacts with the μ-Opioid Receptor and Facilitates Receptor Endocytosis and Recycling

Ist Teil von

• The Journal of biological chemistry, 2007-07, Vol.282 (30), p.22239-22247

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2007

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 μ-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 μ-opioid receptors. On the other hand, overexpression of a M6a-negative mutant prevents μ-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 δ-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.