Journal article
A direct role for arrestins in desensitization of the luteinizing hormone/choriogonadotropin receptor in porcine ovarian follicular membranes
Proceedings of the National Academy of Sciences - PNAS, Vol.96(2), pp.493-498
01/19/1999
Handle:
https://hdl.handle.net/2376/115319
PMCID: PMC15164
PMID: 9892661
Abstract
The luteinizing hormone/choriogonadotropin (LH/CG) receptor (R) is a heptahelical R that, upon agonist binding, activates the stimulatory guanine nucleotide-binding protein (G
s
) and the downstream effector adenylyl cyclase (AC). Like other G protein-coupled Rs, the LH/CG R subsequently exhibits reduced agonist-dependent effector activity, or desensitization, in response to saturating agonist. Unlike desensitization of many other G protein-coupled Rs, the
in vivo
desensitization response of LH/CG R-stimulated AC activity of ovarian follicles to the preovulatory surge of LH can be mimicked under cell-free conditions. Based on evidence that porcine ovarian follicular membranes unexpectedly contained β-arrestin-1, the role of arrestins in desensitization of the LH/CG R was investigated. Results showed that neutralizing arrestin antibodies blocked the development of desensitization and that desensitization was rescued with a synthetic peptide corresponding to the antibody-binding epitope on β-arrestin-1. These results suggest that endogenous β-arrestin-1 participates in agonist-dependent desensitization of the LH/CG R. Addition of recombinant purified β-arrestin-1 mimicked human chorionic gonadotrophin to promote desensitization of human chorionic gonadotrophin-stimulated AC activity, in the presence of the ATP phosphorylation antagonist adenylyl-imidodiphosphate, with an ED
50
of ≈0.1 nM. Increased levels of an 87-kDa protein reactive with glycoprotein hormone R-reactive antibody, consistent with the LH/CG R, coimmunoprecipitated with follicular membrane β-arrestin-1 in response to LH/CG R activation compared with unactivated R. Taken together, these results show that ovarian follicles contain membrane-associated β-arrestin-1, that β-arrestin-1 participates in agonist-dependent desensitization of the LH/CG R, and that the trigger for β-arrestin-1 binding to the LH/CG R appears to be R activation.
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Details
- Title
- A direct role for arrestins in desensitization of the luteinizing hormone/choriogonadotropin receptor in porcine ovarian follicular membranes
- Creators
- Sutapa Mukherjee - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611Krzysztof Palczewski - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611Vsevolod Gurevich - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611Jeffrey L Benovic - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611J. Paul Banga - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611Mary Hunzicker-Dunn - Department of Cell and Molecular Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.96(2), pp.493-498
- Academic Unit
- School of Molecular Biosciences
- Publisher
- The National Academy of Sciences
- Identifiers
- 99900547616801842
- Language
- English
- Resource Type
- Journal article