title: The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment.
abstract: Astrin is a mitotic spindle-associated protein required for the correct alignment of all chromosomes at the metaphase plate. Astrin depletion delays chromosome alignment and causes the loss of normal spindle architecture and sister chromatid cohesion before anaphase onset. Here we describe an astrin complex containing kinastrin/SKAP, a novel kinetochore and mitotic spindle protein, and three minor interaction partners: dynein light chain, Plk1, and Sgo2. Kinastrin is the major astrin-interacting protein in mitotic cells, and is required for astrin targeting to microtubule plus ends proximal to the plus tip tracking protein EB1. Cells overexpressing or depleted of kinastrin mislocalize astrin and show the same mitotic defects as astrin-depleted cells. Importantly, astrin fails to localize to and track microtubule plus ends in cells depleted of or overexpressing kinastrin. These findings suggest that microtubule plus end targeting of astrin is required for normal spindle architecture and chromosome alignment, and that perturbations of this pathway result in delayed mitosis and nonphysiological separase activation.
authors.affiliation: Cancer Research UK Centre, University of Liverpool, Liverpool L3 9TA, England, UK.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Dunsch
authors.forename: Emily
authors.initials: E
authors.lastname: Linnane
authors.forename: Francis A
authors.initials: FA
authors.lastname: Barr
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gruneberg
mesh_terms: D000423:Alcian Blue / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D010619:Phenazines / Q000378:metabolism*; D010640:Phenothiazines / Q000378:metabolism*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012118:Resorcinols / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D010619:Phenazines; D010640:Phenothiazines; D011993:Recombinant Fusion Proteins; D012118:Resorcinols; D014404:Tubulin; C034790:astrin; D000423:Alcian Blue