Human Follicle Stimulating Hormone Receptor Lipid Raft Residency is Hormone and Caveolin Dependent

Abstract

Human follicle stimulating hormone (hFSH) is a gonadotropin responsible for the maturation of ovarian follicles in women and production of sperm in men. The receptor (hFSHR) is a G protein‐coupled receptor (GPCR); a class of receptors found embedded in the cell membrane to receive the hormone resulting in initiation of a complex downstream signaling cascade. Through previous research in the Cohen lab, hFSHR has been shown to be located within compartments of the cell membrane known as lipid rafts. Lipid rafts are microdomains of the membrane containing a higher concentration of cholesterol, glycosphingolipids, and a protein known as caveolin. Current research is focused on evaluating the mechanisms and effects of hFSHR lipid raft residency. Using discontinuous sucrose gradients we have shown that hFSH stimulation of an HEK293 cell line stably transfected with hFSHR cDNA results in alteration of hFSHR lipid raft residency in a time dependent manner.To better understand the mechanism and effect of hFSHR lipid raft residency the same cells were treated with a peptide mimetic of transmembrane domain 4 of hFSHR. This peptide includes a sequence consistent with a motif shown in other proteins to interact with caveolin (ϕXϕXXXXϕXXϕ where ϕ is an aromatic amino acid). The putative caveolin interaction motif of hFSHR was synthesized along with the HIV‐TAT leader sequence to allow passage through the membrane. A second peptide where the aromatic amino acids were replaced with leucine was also used. Cells treated with the wild type peptide showed elevated basal signaling in the absence of hFSH, an effect not observed with the mutant peptide.Together, these results suggest that hFSHR residency in lipid rafts is dependent on hormone treatment and interaction with caveolin. Through studying hFSHR lipid raft residency and signaling we hope to identify ways to control the receptor for improved methods for contraception and treatment of infertility.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.