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Heterotrimeric G proteins demonstrate differential sensitivity to beta-arrestin dependent desensitization.
- Source :
-
Cellular signalling [Cell Signal] 2009 Jul; Vol. 21 (7), pp. 1135-42. Date of Electronic Publication: 2009 Mar 09. - Publication Year :
- 2009
-
Abstract
- 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 beta2 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 Galphaq and Galphas) is recruited to a V2 vasopressin receptor mutant that is constitutively desensitized by beta-arrestin. Interestingly, co-expression of Galpha15 partially rescued cell surface localization and signalling capabilities of the same mutant receptor and reduced beta2 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.
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
Humans
Intracellular Space metabolism
Mutant Proteins metabolism
Protein Transport
Receptors, Adrenergic, beta-2 metabolism
Receptors, Opioid, delta metabolism
Receptors, Vasopressin metabolism
Signal Transduction
beta-Arrestins
Arrestins metabolism
Heterotrimeric GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3913
- Volume :
- 21
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 19275934
- Full Text :
- https://doi.org/10.1016/j.cellsig.2009.03.002