The ADP ribosylation factor nucleotide exchange factor ARNO promotes β-arrestin release necessary for luteinizing hormone/choriogonadotropin receptor desensitization

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dc.creatorMukherjee, Sutapa
dc.creatorGurevich, Vsevolod V.
dc.creatorJones, Jonathan C. R.
dc.creatorCasanova, James E.
dc.creatorFrank, Scott R.
dc.creatorMaizels, Evelyn T.
dc.creatorBader, Marie-France
dc.creatorKahn, Richard A.
dc.creatorPalczewski, Krzysztof
dc.creatorAktories, Klaus
dc.creatorHunzicker-Dunn, Mary
dc.date2000-05-16
dc.date.accessioned2026-08-02T19:50:15Z
dc.descriptionDesensitization of guanine nucleotide binding protein-coupled receptors is a ubiquitous phenomenon characterized by declining effector activity upon persistent agonist stimulation. The luteinizing hormone/choriogonadotropin receptor (LH/CGR) in ovarian follicles exhibits desensitization of effector adenylyl cyclase activity in response to the mid-cycle surge of LH. We have previously shown that uncoupling of the agonist-activated LH/CGR from the stimulatory G protein (G(s)) is dependent on GTP and attributable to binding of β-arrestin present in adenylyl cyclase-rich follicular membrane fraction to the third intracellular (3i) loop of the receptor. Here, we report that LH/CGR-dependent desensitization is mimicked by ADP ribosylation factor nucleotide-binding site opener, a guanine nucleotide exchange factor of the small G proteins ADP ribosylation factors (Arfs) 1 and 6, and blocked by synthetic N-terminal Arf6 peptide, suggesting that the GTP-dependent step of LH/CGR desensitization is receptor-dependent Arf6 activation. Arf activation by GTP and ADP ribosylation factor nucelotide-binding site opener promotes the release of docked β-arrestin from the membrane, making β-arrestin available for LH/CGR; Arf6 but not Arf1 peptides block β-arrestin release from the membrane. Thus, LH/CGR appears to activate two membrane delimited signaling cascades via two types of G proteins: heterotrimeric G(s) and small G protein Arf6. Arf6 activation releases docked β-arrestin necessary for receptor desensitization, providing a feedback mechanism for receptor self-regulation.
dc.identifierhttps://pmc.ncbi.nlm.nih.gov/articles/PMC18531/
dc.identifierhttps://pubmed.ncbi.nlm.nih.gov/10811902/
dc.identifierhttps://doi.org/10.1073/pnas.100127097
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/78772
dc.languageen
dc.publisherNational Academy of Sciences
dc.rightsCopyright © The National Academy of Sciences
dc.sourceProc Natl Acad Sci U S A
dc.subjectBiological Sciences
dc.titleThe ADP ribosylation factor nucleotide exchange factor ARNO promotes β-arrestin release necessary for luteinizing hormone/choriogonadotropin receptor desensitization
dc.typeText

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