Regulation of Ras-signaling pathways by SynGAP

California Institute Of Technology, Pasadena CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The overall objective of this project is to further elucidate the role of SynGAP, a synapse specific Ras GTPase activating protein, in the regulation of activity-dependent Ras activation and downstream Ras effectors. The specific aims are to (1) determine if homeostasis of active Ras is perturbed in the absence of SynGAP in mature synapses, (2) examine whether regulation of actin remodeling through a Ras/PI3K/Rac pathway is influenced by SynGAP activity, and (3) test whether phosphorylation of KV4.2 channels via the Ras/MAPK pathway is altered by disruption of SynGAP activity. The research methods will include techniques routinely performed in the Kennedy lab (Ras activation assays, western immunoblotting, immunocytochemistry, and confocal microscopy) combined with techniques that I learned during my graduate work (hippocampal slice preparation and electrophysiology). Abnormal regulation of Ras and its downstream effectors has been implicated in several human cognitive disorders including Neurefibromatosis, Coffin-Lowry Syndrome, Rubinstein-Taybi Syndrome, and Fragile X Syndrome. Understanding how Ras signaling pathways are regulated in adult neurons may further our understanding of the molecular underpinnings of these disorders.