As abnormalities in neuronal plasticity have been implicated in a wide variety of neurological and psychiatric disorders, one of the top priorities of neuroscience research is to decipher the molecular mechanisms that regulate this process. Recent studies have focused attention on the dynamic changes in neuronal morphology that appear to play an integral role in neuronal plasticity. Although the signaling pathways that mediate and regulate changes in neuronal morphology are poorly understood, recent studies indicate that the Rho family of GTPases play an important in this process. Accordingly, studies aimed at elucidating the regulation and function of these key signaling molecules in neurons are warranted. This R03 application seeks funds to conduct exploratory studies aimed at gaining clues to the function of Tech, a novel brain cDNA isolated by our laboratory. Preliminary studies indicate that the Tech transcript is enriched in cortex and hippocampus and is expressed in neurons. Analysis of the Tech cDNA sequence indicates that it is a member of the Rho GEF family of proteins that regulate the activity of Rho GTPases. Thus, elucidating the function of Tech is likely to provide new insights into the regulation and function of Rho signaling pathways in neurons, an important area of investigation. To explore the function of Tech, we plan to: 1) determine whether the Tech transcript encodes a functional Rho GEF as predicted by its cDNA sequence, 2) define the localization of Tech protein within neurons, and 3) carry out the initial phases of experiments aimed at identifying partner proteins that bind to its putative C-terminal PDZ ligand motif.
| Estevez, Marcel A; Henderson, Jennifer A; Ahn, David et al. (2008) The neuronal RhoA GEF, Tech, interacts with the synaptic multi-PDZ-domain-containing protein, MUPP1. J Neurochem 106:1287-97 |
