Figure 3.

Proposed models of the mechanism by which BAR domain competition creates an edge detector for localized signaling events. (A) In this case, BAR domain proteins act to inhibit endocytosis and signaling across the plasma membrane. Upon ligand binding, activation of the receptor leads to the inactivation of the negative BAR protein and the relocalization or activation of the positive BAR proteins. This allows for the spatial localization of receptor activation and internalization at the point of highest ligand concentration, without inappropriate signaling events occurring laterally across the entirety of the membrane. This also leads to the creation of outward cellular projections and cytoskeletal remodeling in the direction of the guidance cue, leading to correct directional cell migration. (B) In a wildtype state, BAR protein a (purple) acts to inhibit endocytosis across the plasma membrane. Upon ligand binding and receptor activation, the inhibition provided by BAR protein A is overridden and internalization of the cargo proceeds. Internalization of the cargo is aided by BAR protein B (blue). An edge is setup between the two different BAR proteins such that internalization of the cargo only occurs where BAR protein B is active and BAR protein A has been inactivated. (C) After internalization of the cargo or activated receptor, BAR proteins act to specify the subcellular localization of the newly formed vesicle. The specific subcellular relocalization of that vesicle is dependent on the BAR protein(s) that bind to the vesicle membrane.