Journal
CELLULAR SIGNALLING
Volume 21, Issue 7, Pages 1135-1142Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.03.002
Keywords
G15; G protein-coupled receptor; Desensitization; Arrestin; GRK
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Funding
- Italian Ministry of University and Research (MiUR) [RBIN04CKYN]
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G15 is a heterotrimeric G protein of the Gq/11 family. In this study, we describe its exceptional poor sensitivity to the general regulatory mechanism of G protein-coupled receptor (GPCR) desensitization. Enhancing beta 2 adrenergic receptor desensitization by arrestin overexpression, did not affect signalling to G15. Similarly, increased levels of arrestin did not affect G15 signalling triggered by the activation of V2 vasopressin and delta opioid receptors. Furthermore, co-immunoprecipitation experiments showed that G15 alpha subunit (as opposed to G alpha q and G alpha s) is recruited to a V2 vasopressin receptor mutant that is constitutively desensitized by beta-arrestin. Interestingly, co-expression of G alpha 15 partially rescued cell surface localization and signalling capabilities of the same mutant receptor and reduced beta 2 adrenergic receptor internalization. Taken together, these findings provide evidence for a novel mechanism whereby GPCR desensitization can be bypassed and G15 can support sustained signalling in cells chronically exposed to hormones or neurotransmitters. (C) 2009 Elsevier Inc. All rights reserved.
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