Integrin trafficking regulated by Rab21 is necessary for cytokinesis.
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.
Pellinen
Teijo
T
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
Tuomi
Saara
S
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
Arjonen
Antti
A
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
Wolf
Maija
M
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.
Edgren
Henrik
H
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.
Meyer
Hannelore
H
Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
Grosse
Robert
R
Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
Kitzing
Thomas
T
Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
Rantala
Juha K
JK
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
Kallioniemi
Olli
O
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.
Fässler
Reinhard
R
Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
Kallio
Marko
M
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
Ivaska
Johanna
J
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland. Electronic address: johanna.ivaska@vtt.fi.
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D048749:Cytokinesis / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D019096:Vitronectin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D039001:Integrin alpha Chains; D019012:Integrin beta1; D007797:Laminin; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; C415145:RAB21 protein, human; D020691:rab GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein