title: Kinetochore microtubule dynamics and attachment stability are regulated by Hec1.
abstract: Mitotic cells face the challenging tasks of linking kinetochores to growing and shortening microtubules and actively regulating these dynamic attachments to produce accurate chromosome segregation. We report here that Ndc80/Hec1 functions in regulating kinetochore microtubule plus-end dynamics and attachment stability. Microinjection of an antibody to the N terminus of Hec1 suppresses both microtubule detachment and microtubule plus-end polymerization and depolymerization at kinetochores of PtK1 cells. Centromeres become hyperstretched, kinetochore fibers shorten from spindle poles, kinetochore microtubule attachment errors increase, and chromosomes severely mis-segregate. The N terminus of Hec1 is phosphorylated by Aurora B kinase in vitro, and cells expressing N-terminal nonphosphorylatable mutants of Hec1 exhibit an increase in merotelic attachments, hyperstretching of centromeres, and errors in chromosome segregation. These findings reveal a key role for the Hec1 N terminus in controlling dynamic behavior of kinetochore microtubules.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. jgdeluca@email.unc.edu
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: DeLuca
authors.forename: Walter E
authors.initials: WE
authors.lastname: Gall
authors.forename: Claudio
authors.initials: C
authors.lastname: Ciferri
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimini
authors.forename: Andrea
authors.initials: A
authors.lastname: Musacchio
authors.forename: E D
authors.initials: ED
authors.lastname: Salmon
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001704:Biopolymers; D003598:Cytoskeletal Proteins; D018604:Epitope Mapping; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000911:Antibodies, Monoclonal; D001704:Biopolymers; C497850:CLASP1 protein, human; D003598:Cytoskeletal Proteins; C091489:KIF2C protein, human; D008869:Microtubule-Associated Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; C484695:SPC24 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins