Cell migration: GAPs between membrane traffic and the cytoskeleton

During cell migration, coordination between membrane traffic, cell substrat e adhesion and actin reorganization is required for protrusive activity to occur at the leading edge. Actin organization is regulated by Rho family GT Pases and, with a contribution from the endocytic cycle, serves to extend t he cell front. The details of the molecular mechanisms that direct membrane traffic at sites of adhesion and rearrange actin at the cell edge are stil l unknown, However, recent findings show that a number of multi-domain prot eins characterized by an ArfGAP domain interact with both actin-regulating and integrin-binding proteins, as well as affecting Rac-mediated protrusive activity and cell migration. Some of these proteins have been shown to loc alize to endocytic compartments and to have a role in regulating endocytosi s. Given the participation of Arf proteins in regulating membrane traffic, one appealing hypothesis is that the ArfGAPs act as molecular devices that coordinate membrane traffic and cytoskeletal reorganization during cell mot ility.