WASP family proteins are involved in cortical actin cytoskeleton reorganization. Neural Wiskott-Aldrich syndrome protein (N-WASP), a ubiquitously expressed WASP homologous protein, directly binds with Cdc42, activating Arp2/3 complex. In this study, we show that N-WASP-dependent microspike formation is inhibited by formin binding protein 11 (FBP11). Endogenous FBP11 localizes with nuclear-speckles, and co-localization of N-WASP and FBP11 was observed when they were co-expressed. Epidermal growth factor (EGF) induced actin-microspike formation in COS7 cells. However, transient expression of FBP11 suppressed N-WASP-dependent actin-microspike formation by trapping N-WASP in the nucleus. These results indicate that FBP11 regulates localization of N-WASP, thus negatively regulating the function of N-WASP in the cytoplasm. (C) 2003 Elsevier Inc. All rights reserved.