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)

Research output: Contribution to journalArticleScientificpeer-review

132 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
Number of pages15
JournalDevelopmental Cell
Volume15
Issue number3
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Cytokinesis
Integrins
Cells
Cell Division
Monomeric GTP-Binding Proteins
Genomic Instability
Cell adhesion
Endocytosis
Gene expression
Cell Adhesion
Machinery
Neoplasms
Adhesion
Phenotype
Gene Expression
Defects

Keywords

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

Cite this

Pellinen, T., Tuomi, S., Arjonen, A., Wolf, M., Edgren, H., Meyer, H., ... 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
Pellinen, Teijo ; Tuomi, Saara ; Arjonen, Antti ; Wolf, Maija ; Edgren, Henrik ; Meyer, Hannelore ; Grosse, Robert ; Kitzing, Thomas ; Rantala, Juha K. ; Kallioniemi, Olli ; Fässler, Reinhard ; Kallio, Marko ; Ivaska, Johanna. / Integrin trafficking regulated by Rab21 is necessary for cytokinesis. In: Developmental Cell. 2008 ; Vol. 15, No. 3. pp. 371-385.
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Pellinen, T, Tuomi, S, Arjonen, A, Wolf, M, Edgren, H, Meyer, H, Grosse, R, Kitzing, T, Rantala, JK, Kallioniemi, O, Fässler, R, Kallio, M & Ivaska, J 2008, 'Integrin trafficking regulated by Rab21 is necessary for cytokinesis', Developmental Cell, vol. 15, no. 3, pp. 371-385. https://doi.org/10.1016/j.devcel.2008.08.001

Integrin trafficking regulated by Rab21 is necessary for cytokinesis. / Pellinen, Teijo; Tuomi, Saara; Arjonen, Antti; Wolf, Maija; Edgren, Henrik; Meyer, Hannelore; Grosse, Robert; Kitzing, Thomas; Rantala, Juha K.; Kallioniemi, Olli; Fässler, Reinhard; Kallio, Marko; Ivaska, Johanna (Corresponding Author).

In: Developmental Cell, Vol. 15, No. 3, 2008, p. 371-385.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Integrin trafficking regulated by Rab21 is necessary for cytokinesis

AU - Pellinen, Teijo

AU - Tuomi, Saara

AU - Arjonen, Antti

AU - Wolf, Maija

AU - Edgren, Henrik

AU - Meyer, Hannelore

AU - Grosse, Robert

AU - Kitzing, Thomas

AU - Rantala, Juha K.

AU - Kallioniemi, Olli

AU - Fässler, Reinhard

AU - Kallio, Marko

AU - Ivaska, Johanna

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

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Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H et al. Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Developmental Cell. 2008;15(3):371-385. https://doi.org/10.1016/j.devcel.2008.08.001