title: An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin.
abstract: Mitosis requires precise control of microtubule dynamics. The KinI kinesin MCAK, a microtubule depolymerase, is critical for this regulation. In a screen to discover previously uncharacterized microtubule-associated proteins, we identified ICIS, a protein that stimulates MCAK activity in vitro. Consistent with this biochemical property, blocking ICIS function in Xenopus extracts with antibodies caused excessive microtubule growth and inhibited spindle formation. Prior to anaphase, ICIS localized in an MCAK-dependent manner to inner centromeres, the chromosomal region located in between sister kinetochores. From Xenopus extracts, ICIS coimmunoprecipitated MCAK and the inner centromere proteins INCENP and Aurora B, which are thought to promote chromosome biorientation. By immunoelectron microscopy, we found that ICIS is present on the surface of inner centromeres, placing it in an ideal location to depolymerize microtubules associated laterally with inner centromeres. At inner centromeres, MCAK-ICIS may destabilize these microtubules and provide a mechanism that prevents kinetochore-microtubule attachment errors.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ryoma_ohi@hms.harvard.edu
authors.forename: Ryoma
authors.initials: R
authors.lastname: Ohi
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Coughlin
authors.forename: William S
authors.initials: WS
authors.lastname: Lane
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchison
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002503:Centromere / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism; D014020:Tissue Extracts; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; C477651:MTUS1 protein, Xenopus; D008869:Microtubule-Associated Proteins; D044786:S-Phase Kinase-Associated Proteins; D014020:Tissue Extracts; D029867:Xenopus Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins