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Beta‐arrestin 1 and beta‐arrestin 2 differentially direct the phosphorylation‐dependent and ‐independent internalization and desensitization of delta‐opioid receptor
Author(s) -
Qiu Yu,
Kouhen Odile MaestriEl,
Loh Horace H.,
Law PingYee
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a251-b
Subject(s) - internalization , desensitization (medicine) , enkephalin , microbiology and biotechnology , phosphorylation , arrestin , biology , δ opioid receptor , receptor , g protein coupled receptor , medicine , endocrinology , chemistry , signal transduction , opioid , biochemistry
δ‐opioid receptor (DOR) and its phosphorylation‐deficient mutant S363A (DORS363A) underwent internalization and desensitization during the long‐term activation by [D‐Pen 2 ,D‐Pen 5 ]enkephalin (DPDPE). Co‐expression of dominant negative mutant of dynamin (DynK44E) blocked the internalization of both DOR and DORS363A without significant influence on their desensitization. Confocal microscopy studies using β‐arrestinGFP indicated that both DOR and DORS363A activation could induce transient translocation of the β‐arrestins to the plasma membrane. Internalization and desensitization of both DOR and its phosphorylation‐deficient mutant DTS were blocked in mouse embryonic fibroblasts (MEF) cells lacking β‐arrestin1 and β‐arrestin 2 (β arr1 −/− /β arr2 −/− ) upon long‐term treatment of DPDPE, suggesting that β‐arrestins is a key determinant in triggering receptor desensitization. Internalization of DOR was impaired similarly in MEF cells lacking β‐arr1 (β arr1 −/− ) or cells lacking β‐arr2 (β arr2 −/− ). However, desensitization of DOR in β arr1 −/− cells was slightly reduced, while the desensitization of DOR was significantly impaired in β arr2 −/− cells. On the other hand, both internalization and desensitization of DTS is not significantly impaired in both β arr1 −/− and β arr2 −/− cells. These results indicate that β‐arrestin 1 and β‐arrestin 2 are differentially required in the phosphorylation‐dependent and ‐independent internalization and desensitization of DOR. (These studies are supported by NIDA grants DA007339, DA016674, DA000564, DA011806)