title: Integrin trafficking regulated by Rab21 is necessary for cytokinesis.
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.
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
authors.forename: Teijo
authors.initials: T
authors.lastname: Pellinen
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Tuomi
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Arjonen
authors.affiliation: 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.
authors.forename: Maija
authors.initials: M
authors.lastname: Wolf
authors.affiliation: 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.
authors.forename: Henrik
authors.initials: H
authors.lastname: Edgren
authors.affiliation: Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Meyer
authors.affiliation: Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Grosse
authors.affiliation: Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kitzing
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
authors.forename: Juha K
authors.initials: JK
authors.lastname: Rantala
authors.affiliation: 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.
authors.forename: Olli
authors.initials: O
authors.lastname: Kallioniemi
authors.affiliation: Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Kallio
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Turku FIN-20520, Finland. Electronic address: johanna.ivaska@vtt.fi.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
mesh_terms: 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
chemical_list: 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