EFC/F-BAR proteins and the N-WASP–WIP complex induce membrane curvature-dependent actin polymerization

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Abstract
Extended Fer‐CIP4 homology (EFC)/FCH‐BAR (F‐BAR) domains generate and bind to tubular membrane structures of defined diameters that are involved in the formation and fission of endocytotic vesicles. Formin‐binding protein 17 (FBP17) and Toca‐1 contain EFC/F‐BAR domains and bind to neural Wiskott–Aldrich syndrome protein (N‐WASP), which links phosphatidylinositol (4,5)‐bisphosphate (PIP2) and the Rho family GTPase Cdc42 to the Arp2/3 complex. The N‐WASP–WASP‐interacting protein (WIP) complex, a predominant form of N‐WASP in cells, is known to be activated by Toca‐1 and Cdc42. Here, we show that N‐WASP–WIP complex‐mediated actin polymerization is activated by phosphatidylserine‐containing membranes depending on membrane curvature in the presence of Toca‐1 or FBP17 and in the absence of Cdc42 and PIP2. Cdc42 further promoted the activation of actin polymerization by N‐WASP–WIP. Toca‐1 or FBP17 recruited N‐WASP–WIP to the membrane. Conserved acidic residues near the SH3 domain of Toca‐1 and FBP17 positioned the N‐WASP–WIP to be spatially close to the membrane for activation of actin polymerization. Therefore, curvature‐dependent actin polymerization is stimulated by spatially appropriate interactions of EFC/F‐BAR proteins and the N‐WASP–WIP complex with the membrane.