Integrin trafficking regulated by Rab21 is necessary for cytokinesis

Dev Cell. 2008 Sep;15(3):371-85. doi: 10.1016/j.devcel.2008.08.001.

Abstract

Adherent cells undergo remarkable changes in shape during cell division. However, the functional interplay between cell adhesion turnover and the mitotic machinery is poorly understood. The endo/exocytic trafficking of integrins is regulated by the small GTPase Rab21, which associates with several integrin alpha subunits. Here, we show that targeted trafficking of integrins to and from the cleavage furrow is required for successful cytokinesis, and that this is regulated by Rab21. Rab21 activity, integrin-Rab21 association, and integrin endocytosis are all necessary for normal cytokinesis, which becomes impaired when integrin-mediated adhesion at the cleavage furrow fails. We also describe a chromosomal deletion and loss of Rab21 gene expression in human cancer, which leads to the accumulation of multinucleate cells. Importantly, reintroduction of Rab21 rescued this phenotype. In conclusion, Rab21-regulated integrin trafficking is essential for normal cell division, and its defects may contribute to multinucleation and genomic instability, which are hallmarks of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Adhesion / physiology
  • Cell Cycle / physiology
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Cytokinesis / physiology*
  • Endocytosis / physiology
  • Humans
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism*
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Laminin / metabolism
  • Mice
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Vitronectin / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Integrin alpha Chains
  • Integrin beta1
  • Laminin
  • Recombinant Fusion Proteins
  • Vitronectin
  • RAB21 protein, human
  • rab GTP-Binding Proteins
  • rhoA GTP-Binding Protein