Cdc42, a member of the Rho subfamily of Ras GTPases, is involved in a number of biological pathways, such as cell growth and differentiation, actin cytoskeleton dynamics, and cell motility. To understand how Cdc42 can control these widely different processes, the effector pathways it activates must be examined. One such pathway that has not been extensively studied is Cdc42's activation of the Borg family of proteins. This proposal will examine the mechanisms of Borg regulation and how this regulation impacts on a family of known Borg binding proteins, the mammalian Septins.
Specific aim #1 will identify potential signaling pathways involved in Borg regulation, focusing on my recent discovery that Borgs are phosphorylated in vivo.
This aim will be accomplished by determining the site(s) phosphorylated on Borgs, the signal transduction cascades that stimulate Borg phosphorylation, and the effect of overexpressing Borg phosphorylation site mutants on its localization and on cell morphology.
Specific aim #2 will build on the knowledge obtained in aim #1 to examine the role of Borgs in Septin organization and function. Septins can interact with one another to form filaments. The effect of Borg phosphorylation on its binding to Septins, Septin organization in the cell, and Septin control of cytokinesis will be examined.
