期刊
DEVELOPMENTAL CELL
卷 15, 期 3, 页码 371-385出版社
CELL PRESS
DOI: 10.1016/j.devcel.2008.08.001
关键词
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资金
- Academy of Finland
- innish Cancer Organizations
- Sigrid Juselius Foundation
- Emil Aaltonen Foundation
- European Molecular Biology Organization Young Investigator Program
- Max Planck Society
- Marie Curie Excellence [002697 MK, 0027280K]
- Emmy Noether Program of the Deutsche Forschungsgemeinschaft
- GR 2111/1-3
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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