2. Academic Validation
  3. Integrin trafficking regulated by Rab21 is necessary for cytokinesis

Integrin trafficking regulated by Rab21 is necessary for cytokinesis

  • Dev Cell. 2008 Sep;15(3):371-385. doi: 10.1016/j.devcel.2008.08.001.
Teijo Pellinen 1,  Saara Tuomi 1,  Antti Arjonen 1,  Maija Wolf 2,  Henrik Edgren 2,  Hannelore Meyer 3,  Robert Grosse 4,  Thomas Kitzing 4,  Juha K Rantala 1,  Olli Kallioniemi 2,  Reinhard Fässler 3,  Marko Kallio 1,  Johanna Ivaska 5
Affiliations

Affiliations

  • 1 Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
  • 2 Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland; FIMM, Institute of Molecular Medicine and the Genome-Scale Biology Research Program, Biomedicum, 00014 University of Helsinki, Helsinki, Finland.
  • 3 Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
  • 4 Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
  • 5 Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland. Electronic address: [email protected].
PMID: 18804435 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.

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