title: FBP11 regulates nuclear localization of N-WASP and inhibits N-WASP-dependent microspike formation.
abstract: 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.
authors.affiliation: Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Mizutani
authors.forename: Shiro
authors.initials: S
authors.lastname: Suetsugu
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D020224:Expressed Sequence Tags; D005982:Glutathione Transferase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000737:chemistry*; D013058:Mass Spectrometry; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D010940:Plant Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein / Q000737:chemistry
chemical_list: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D010940:Plant Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C097416:floral-binding protein 11, Petunia; D005982:Glutathione Transferase; D020764:cdc42 GTP-Binding Protein