BAR domain proteins regulate Rho GTPase signaling

Abstract

BAR proteins comprise a heterogeneous group of multi-domain proteins with diverse biological functions. The common denominator is the Bin-Amphiphysin-Rvs (BAR) domain that not only confers targeting to lipid bilayers, but also provides scaffolding to mold lipid membranes into concave or convex surfaces. This function of BAR proteins is an important determinant in the dynamic reconstruction of membrane vesicles, as well as of the plasma membrane. Several BAR proteins function as linkers between cytoskeletal regulation and membrane dynamics. These links are provided by direct interactions between BAR proteins and actin-nucleation-promoting factors of the Wiskott-Aldrich syndrome protein family and the Diaphanous-related formins. The Rho GTPases are key factors for orchestration of this intricate interplay. This review describes how BAR proteins regulate the activity of Rho GTPases, as well as how Rho GTPases regulate the function of BAR proteins. This mutual collaboration is a central factor in the regulation of vital cellular processes, such as cell migration, cytokinesis, intracellular transport, endocytosis, and exocytosis.

Keywords: BAR domain; F-BAR; Rho GTPases; actin; membrane trafficking.

Figure 1.

Schematic representations of the BAR-protein-mediated regulation of the Rho GTPases. (A) BAR proteins with a RhoGEF domain directly activate Rho GTPases. (B) BAR proteins with a RhoGAP domain directly increase the intrinsic hydrolysis activity of Rho GTPases, thereby inhibiting their activity. (C) BAR proteins with a Rho-binding domain sequester the activated GTP-bound form of Rho GTPases, thereby resulting in a decrease in the active GTP-bound Rho GTPase.

Figure 2.

Schematic representation of the coordination of the machinery involved in the regulation of membrane dynamics and the factors that regulate cytoskeletal reorganization.