Integrin trafficking regulated by Rab21 is necessary for cytokinesis

Teijo Pellinen, Saara Tuomi, Antti Arjonen, Maija Wolf, Henrik Edgren, Hannelore Meyer, Robert Grosse, Thomas Kitzing, Juha K. Rantala, Olli Kallioniemi, Reinhard Fässler, Marko Kallio, Johanna Ivaska (Corresponding Author)

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136 Citations (Scopus)

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 α 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.
Original languageEnglish
Pages (from-to)371-385
JournalDevelopmental Cell
Volume15
Issue number3
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Keywords

  • cytokinesis
  • integrin
  • cell adhesion
  • cell division
  • genomic instability
  • multinucleation
  • cancer
  • Rab21

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  • Cite this

    Pellinen, T., Tuomi, S., Arjonen, A., Wolf, M., Edgren, H., Meyer, H., Grosse, R., Kitzing, T., Rantala, J. K., Kallioniemi, O., Fässler, R., Kallio, M., & Ivaska, J. (2008). Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Developmental Cell, 15(3), 371-385. https://doi.org/10.1016/j.devcel.2008.08.001