title: mDia1 and WAVE2 proteins interact directly with IRSp53 in filopodia and are involved in filopodium formation.
abstract: Filopodia are dynamic actin-rich cell surface protrusions involved in cell migration, axon guidance, and wound healing. The RhoGTPase Cdc42 generates filopodia via IRSp53, a multidomain protein that links the processes of plasma membrane deformation and actin dynamics required for their formation in mammalian cells. The Src homology 3 domain of IRSp53 binds to the actin regulators Mena, Eps8, WAVE1, WAVE2, mDia1, and mDia2. We show that mDia1 and WAVE2 synergize with IRSp53 to form filopodia. IRSp53 also interacts directly with these two proteins within filopodia, as observed in acceptor photobleaching FRET studies. Measurement of filopodium formation by time-lapse imaging of live cells also revealed that depleting neuronal cells of either mDia1 or WAVE2 protein decreases the ability of IRSp53 to induce filopodia. In contrast, IRSp53 does not appear to partner WAVE1 or mDia2 to give rise to these structures. In addition, although all three isoforms of mDia are capable of inducing filopodia, IRSp53 requires only mDia1 to do so. These findings suggest that mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia.
authors.affiliation: Institute of Medical Biology, 8A Biomedical Grove, Immunos, Singapore 138655.
authors.forename: Wah Ing
authors.initials: WI
authors.lastname: Goh
authors.forename: Kim Buay
authors.initials: KB
authors.lastname: Lim
authors.forename: Thankiah
authors.initials: T
authors.lastname: Sudhaharan
authors.forename: Kai Ping
authors.initials: KP
authors.lastname: Sem
authors.forename: Wenyu
authors.initials: W
authors.lastname: Bu
authors.forename: Ai Mei
authors.initials: AM
authors.lastname: Chou
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism*; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C119539:BAIAP2 protein, human; C539986:Baiap2 protein, mouse; D002352:Carrier Proteins; C108962:DIAPH1 protein, human; C491464:Diap1 protein, mouse; D000080865:Formins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C114864:WASF1 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D020764:cdc42 GTP-Binding Protein