MECHANISM AND REGULATION OF RECEPTOR-G PROTEIN SIGNALING

Washington University, Saint Louis MO

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Abstract

PROJECT SUMMARY/ABSTRACT The long-term goal of this project is to define mechanisms that govern signal transduction by G protein-coupled receptors (GPCRs). The focus of the present application is a class of developmentally-regulated, visual and nervous system-specific G¿¿ dimers consisting of G¿5, the most diverged and least understood G¿ family member, bound to the G¿-like domain of any member of the RGS7 (R7) family of G protein regulators. R7-G¿5 heterodimers bind R7BP, a novel palmitoylated SNARE-like protein. The central hypothesis of this application is that palmitate cycling on R7BP controls the localization and function of R7-G¿5-R7BP complexes as regulators of neuronal structure and function. This project will test this hypothesis by employing interdisciplinary cell, molecular and electrophysiological assays that address the following Specific Aims: 1) identify mechanisms that regulate R7BP palmitate cycling and trafficking in primary neurons; 2) determine how R7BP regulates the ability of R7- G¿5 complexes to modulate synaptic transmission and the role of palmitoylation in these processes; and 3) identify signaling mechanisms whereby R7-G¿5-R7BP complexes regulate neuronal development, plasticity and morphogenesis.