β-arrestins and biased signaling in gonadotropin receptors

Minerva ginecologica
Francesco De Pascali, Eric Reiter

Abstract

Gonadotropin receptors include the follicle stimulating hormone receptor (FSHR) and the luteinizing hormone/choriogonadotropin receptor (LHCGR), both belong to the G protein-coupled receptor (GPCR) superfamily and are essential to reproduction. FSHR is activated by follicle stimulating hormone (FSH) while LHCGR is activated by either luteinizing hormone (LH) or choriogonadotropin (CG). Upon ligand binding, gonadotropin receptors undergo conformational changes that lead to the activation of the heterotrimeric G protein, resulting in the production of different second messengers. Gonadotropin receptors can also recruit and bind β-arrestins. This particular class of scaffold proteins were initially identified to mediate GPCRs desensitization and recycling, but it is now well established that β-arrestins can also initiate Gs-independent signaling by assembling signaling modules. Furthermore, new advances in structural biology and biophysical techniques have revealed novel activation mechanisms allowing β-arrestins and G proteins to control signaling in time and space. The ability of different ligands to preferentially elicit G- or β-arrestin-mediated signaling is known as functional selectivity or biased signaling. This new concept...Continue Reading

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Citations

Feb 23, 2019·Frontiers in Endocrinology·Rosemary McDonaldT Rajendra Kumar
Sep 29, 2018·International Journal of Molecular Sciences·Hanne LeysenStuart Maudsley
Mar 6, 2019·Frontiers in Endocrinology·Elodie KaraMarie-Christine Maurel
May 30, 2019·Frontiers in Endocrinology·Livio Casarini, Pascale Crépieux
Apr 2, 2019·Frontiers in Endocrinology·Flavie LandomielEric Reiter
Oct 22, 2020·Molecular Human Reproduction·Livio CasariniManuela Simoni
Dec 21, 2021·Frontiers in Endocrinology·Uchechukwu T AgwuegboKim C Jonas

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