The long-term goal of the proposed research is to understand the mechanisms involved in cellular motility. The ability of cells to move is central to a myriad of physiological processes including embryonic development, neural network formation, immune function, and metastisis. The project focuses on a multi-protein complex, the Arp2/3 complex, that appears to play a central role in lamellipodial cell motility. Initial studies will address the mechanisms by which Arp2/3 function is regulated, with particular attention to phosphorylation. These studies will test the effects of phosphorylation both in mammalian cells and in cell-free assays. Subsequent studies will focus on the pathways by which this regulation occurs, with focus on Rho family GTPases. In addition, Arp2/3 complex interacting factors will be identified. Finally, the reasons for the existence of isoforms for one of the Arp2/3 complex subunits will be addressed.
