Control of Rho GTPase function by BAR-domains

Cytoskeletal dynamics are key to the establishment of cell polarity and the consequent coordination of protrusion and contraction that drives cell migration. During these events, the actin and microtubule cytoskeleton act in concert with the cellular machinery that controls endo-and exocytosis, thus regulating polarized traffic of membranes and membrane-associated proteins. Small GTPases of the Rho family orchestrate cytoskeletal dynamics. Rho GTPase signaling is tightly regulated and mislocalization or constitutive activation may lead to, for example, morphogenetic abnormalities, tumor cell metastasis or apoptosis. There is increasing evidence that traffic to and from the plasma membrane constitutes an important mechanism controlling Rho GTPase activation and signaling. This brief overview discusses a group of proteins that function at the interface between membrane dynamics and RhoGTPase signaling. These proteins all share a so-called BAR domain, which is a lipid and protein binding region that also harbors membrane deforming activity. In the past 15 years, a growing number of BAR domain proteins have been identified and found to regulate Rho GTPase signaling. The studies discussed here define several modes of RhoGTPase regulation through BAR-domain containing proteins, identifying the BAR domain as an important regulatory unit bridging membrane traffic and cytoskeletal dynamics.