title: Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B.
abstract: Numerous scaffold proteins coordinate signals from the environment with actin-based protrusions during shape change and migration. Many scaffolds integrate signals from Rho-family GTPases to effect the assembly of specific actin structures. Here we investigate the mechanism of action MIM-B (missing in metastasis-B) on the actin cytoskeleton. MIM-B binds actin monomer through a WASP homology 2 motif, bundles actin filaments via an IRSp53/MIM domain, and is a long isoform of MIM, a proposed metastasis suppressor. We analysed the activity of MIM-B toward the actin cytoskeleton as well as its potential link to cancer metastasis. Endogenous MIM-B protein is widely expressed and its expression is maintained in various metastatic cell lines. MIM-B induces lamellipodia-like actin-rich protrusions. The IRSp53/MIM domain of MIM-B, as well as Rac activity are required to induce protrusions, but not the WASP homology 2 motif. MIM-B binds and activates Rac via its IRSp53/MIM domain, but this is not sufficient to induce lamellipodia. Finally, our data revealed that actin bundling and Rac-binding properties of MIM-B are not separable. Thus, MIM-B is unlikely to be a metastasis suppressor but acts as a scaffold protein that interacts with Rac, actin and actin-associated proteins to modulate lamellipodia formation.
authors.affiliation: School of Biosciences, Division of Molecular Cell Biology, University of Birmingham, Edgbaston, Birmingham, B15 2TT UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bompard
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Sharp
authors.forename: Gilles
authors.initials: G
authors.lastname: Freiss
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins; D011485:Protein Binding; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D016415:Sequence Alignment; D041701:Swiss 3T3 Cells; D014162:Transfection; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D016895:Culture Media, Serum-Free; C486778:MTSS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C052523:actin filament bundling proteins; D020744:rac GTP-Binding Proteins