title: I-BAR domains, IRSp53 and filopodium formation.
abstract: Filopodia and lamellipodia are dynamic actin-based structures that determine cell shape and migration. Filopodia are thought to sense the environment and direct processes such as axon guidance and neurite outgrowth. Cdc42 is a small GTP-binding protein and member of the RhoGTPase family. Cdc42 and its effector IRSp53 (insulin receptor phosphotyrosine 53 kDa substrate) have been shown to be strong inducers of filopodium formation. IRSp53 consists of an I-BAR (inverse-Bin-Amphiphysin-Rvs) domain, a Cdc42-binding domain and an SH3 domain. The I-BAR domain of IRSp53 induces membrane tubulation of vesicles and dynamic membrane protrusions lacking actin in cells. The IRSp53 SH3 domain interacts with proteins that regulate actin filament formation e.g. Mena, N-WASP, mDia1 and Eps8. In this review we suggest that the mechanism for Cdc42-driven filopodium formation involves coupling I-BAR domain-induced membrane protrusion with SH3 domain-mediated actin dynamics through IRSp53.
authors.affiliation: Neural Stem Cell Laboratory, Institute of Medical Biology, 8A Biomedical Grove, #05-37 Immunos, Singapore 138648, Singapore. sohail.ahmed@imb.a-star.edu.sg
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
authors.forename: Wah Ing
authors.initials: WI
authors.lastname: Goh
authors.forename: Wenyu
authors.initials: W
authors.lastname: Bu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C119539:BAIAP2 protein, human; D009419:Nerve Tissue Proteins; D020764:cdc42 GTP-Binding Protein