Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP

Abstract

Cdc42 is a small GTPase of the Rho family which regulates the formation of actin filaments to generate filopodia¹,². Although there are several proteins such as PAK³, ACK⁴ and WASP (Wiskott–Aldrich syndrome protein)⁵ that bind Cdc42 directly, none of these can account for the filopodium formation induced by Cdc42. Here we demonstrate that before it can induce filopodium formation, Cdc42 must bind a WASP-related protein, N-WASP, that is richest in neural tissues⁶ but is expressed ubiquitously. N-WASP induces extremely long actin microspikes only when co-expressed with active Cdc42, whereas WASP, which is expressed in haematopoietic cells, does not, despite the structural similarities between WASP and N-WASP. In a cell-free system, addition of active Cdc42 significantly stimulates the actin-depolymerizing activity of N-WASP, creating free barbed ends from which actin polymerization can then take place. This activation seems to be caused by exposure of N-WASP's actin-depolymerizing region induced by Cdc42 binding.