Sökning: WFRF:(Hutchinson Dana S.) >
Interaction with Ca...
Interaction with Caveolin-1 Modulates G Protein Coupling of Mouse beta(3)-Adrenoceptor
-
- Sato, Masaaki (författare)
- Stockholms universitet,Avdelningen för fysiologi
-
Hutchinson, Dana S. (författare)
-
Halls, Michelle L. (författare)
-
visa fler...
-
Furness, Sebastian G. B. (författare)
-
- Bengtsson, Tore (författare)
- Stockholms universitet,Avdelningen för fysiologi
-
Evans, Bronwyn A. (författare)
-
Summers, Roger J. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2012
- 2012
- Engelska.
-
Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:24, s. 20674-20688
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Caveolins act as scaffold proteins in multiprotein complexes and have been implicated in signaling by G protein-coupled receptors. Studies using knock-out mice suggest that beta(3)-adrenoceptor (beta(3)-AR) signaling is dependent on caveolin-1; however, it is not known whether caveolin-1 is associated with the beta(3)-AR or solely with downstream signaling proteins. We have addressed this question by examining the impact of membrane rafts and caveolin-1 on the differential signaling of mouse beta(3a)- and beta(3b)-AR isoforms that diverge at the distal C terminus. Only the beta(3b)-AR promotes pertussis toxin (PTX)-sensitive cAMP accumulation. When cells expressing the beta(3a)-AR were treated with filipin III to disrupt membrane rafts or transfected with caveolin-1 siRNA, the cyclic AMP response to the beta(3)-AR agonist CL316243 became PTX-sensitive, suggesting G alpha(i/o) coupling. The beta(3a)-AR C terminus, S (P-384) under bar PLNR (P-389) under bar DG (Y-392) under bar EGARP (P-398) under bar PT, resembles a caveolin interaction motif. Mutant beta(3a)-ARs (F389A/Y392A/F398A or P384S/F389A) promoted PTX-sensitive cAMP responses, and in situ proximity assays demonstrated an association between caveolin-1 and the wild type beta(3a)-AR but not the mutant receptors. In membrane preparations, the beta(3b)-AR activated G alpha(o) and mediated PTX-sensitive cAMP responses, whereas the beta(3a)-AR did not activate G alpha(i/o) proteins. The endogenous beta(3a)-AR displayed G alpha(i/o) coupling in brown adipocytes from caveolin-1 knock-out mice or in wild type adipocytes treated with filipin III. Our studies indicate that interaction of the beta(3a)-AR with caveolin inhibits coupling to G alpha(i/o) proteins and suggest that signaling is modulated by a raft-enriched complex containing the beta(3a)-AR, caveolin-1, G alpha(s), and adenylyl cyclase.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas