Involvement of Rac in actin cytoskeleton rearrangements induced by MIM-B.

  • Bompard G
  • Sharp S
  • Freiss G
 et al. 
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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.

Author-supplied keywords

  • Actins
  • Actins: metabolism
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Cercopithecus aethiops
  • Culture Media, Serum-Free
  • Culture Media, Serum-Free: pharmacology
  • Cytoskeleton
  • Cytoskeleton: chemistry
  • Cytoskeleton: metabolism
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins
  • Microfilament Proteins: chemistry
  • Microfilament Proteins: deficiency
  • Microfilament Proteins: genetics
  • Microfilament Proteins: metabolism
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins
  • Protein Binding
  • Pseudopodia
  • Pseudopodia: drug effects
  • Pseudopodia: metabolism
  • Sequence Alignment
  • Swiss 3T3 Cells
  • Transfection
  • rac GTP-Binding Proteins
  • rac GTP-Binding Proteins: metabolism

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Authors

  • Guillaume Bompard

  • Stewart J Sharp

  • Gilles Freiss

  • Laura M Machesky

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