Castro-Fernández Cecilia, Conn P Michael
Oregon National Primate Research Center and Department of Physiology and Pharmacology, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Mol Cell Endocrinol. 2002 Jun 14;191(2):149-56. doi: 10.1016/s0303-7207(02)00082-5.
The cytoplasmic carboxyl-terminus of G-protein coupled receptors (GPCRs), absent in the mammalian gonadotropin-releasing hormone receptor (GnRHR), plays an important role in receptor expression, desensitization, internalization and efficiency of coupling to G proteins. Regulators of G protein signaling (RGS) likewise are involved in regulating GPCR-G protein mediated responses and can regulate transcription of other genes. In this study, we evaluate differential expression, ligand binding and effector coupling of the rat GnRHR (rGnRHR) and a chimera of rGnRHR with the pre-mammalian carboxyl domain (rGnRHR-C-tail). Membrane expression of the chimeric receptor and G(q)alpha and G(s)alpha-mediated signaling was increased 2- and 1.5-fold, respectively by RGS10, while RGS3 did not interfere with rGnRHR and rGnRHR-C-tail cell surface expression in spite of negatively regulating GnRH-stimulated G(q)alpha-mediated signaling by both receptors. The rGnRHR and rGnRHR-C-tail showed similar internalization rates in the presence of either RGS protein, indicating that the modification of rGnRHR expression and regulation in the presence of a carboxyl-terminus by RGS10 was not caused by alteration of the internalization rate. The observations in this study implicate the carboxyl domain of the receptor as a site of interaction for RGS10, but not RGS3. This is the first evidence of an altered cell surface expression and regulation of the GnRHR bearing a carboxyl-terminus by RGS proteins.
