title: Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis.
abstract: Chromokinesins are microtubule plus end-directed motor proteins that bind to chromosome arms. In Xenopus egg cell-free extracts, Xkid and Xklp1 are essential for bipolar spindle formation but the functions of the human homologues, hKID (KIF22) and KIF4A, are poorly understood. By using RNAi-mediated protein knockdown in human cells, we find that only co-depletion delayed progression through mitosis in a Mad2-dependent manner. Depletion of hKID caused abnormal chromosome arm orientation, delayed chromosome congression, and sensitized cells to nocodazole. Knockdown of KIF4A increased the number and length of microtubules, altered kinetochore oscillations, and decreased kinetochore microtubule flux. These changes were associated with failures in establishing a tight metaphase plate and an increase in anaphase lagging chromosomes. Co-depletion of both chromokinesins aggravated chromosome attachment failures, which led to mitotic arrest. Thus, hKID and KIF4A contribute independently to the rapid and correct attachment of chromosomes by controlling the positioning of chromosome arms and the dynamics of microtubules, respectively.
authors.affiliation: Biocenter, Division of Molecular Pathophysiology, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Wandke
authors.forename: Marin
authors.initials: M
authors.lastname: Barisic
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sigl
authors.forename: Veronika
authors.initials: V
authors.lastname: Rauch
authors.forename: Frank
authors.initials: F
authors.lastname: Wolf
authors.forename: Ana C
authors.initials: AC
authors.lastname: Amaro
authors.forename: Chia H
authors.initials: CH
authors.lastname: Tan
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pereira
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kutay
authors.forename: Helder
authors.initials: H
authors.lastname: Maiato
authors.forename: Patrick
authors.initials: P
authors.lastname: Meraldi
authors.forename: Stephan
authors.initials: S
authors.lastname: Geley
mesh_terms: D000705:Anaphase / Q000502:physiology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D020090:Chromosome Segregation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008677:Metaphase / Q000502:physiology; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C098764:KIF22 protein, human; C490913:KIFF22 protein, Xenopus; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029867:Xenopus Proteins; C092349:chromokinesin; C484228:KIF4A protein, human; D016547:Kinesins