title: An essential step of kinetochore formation controlled by the SNARE protein Snap29.
abstract: The kinetochore is an essential structure that mediates accurate chromosome segregation in mitosis and meiosis. While many of the kinetochore components have been identified, the mechanisms of kinetochore assembly remain elusive. Here, we identify a novel role for Snap29, an unconventional SNARE, in promoting kinetochore assembly during mitosis in Drosophila and human cells. Snap29 localizes to the outer kinetochore and prevents chromosome mis-segregation and the formation of cells with fragmented nuclei. Snap29 promotes accurate chromosome segregation by mediating the recruitment of Knl1 at the kinetochore and ensuring stable microtubule attachments. Correct Knl1 localization to kinetochore requires human or Drosophila Snap29, and is prevented by a Snap29 point mutant that blocks Snap29 release from SNARE fusion complexes. Such mutant causes ectopic Knl1 recruitment to trafficking compartments. We propose that part of the outer kinetochore is functionally similar to membrane fusion interfaces.
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Morelli
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mastrodonato
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Beznoussenko
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Mironov
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Tognon
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy thomas.vaccari@ifom.eu.
authors.forename: Thomas
authors.identifier: 0000-0002-6231-7105
authors.initials: T
authors.lastname: Vaccari
mesh_terms: D000818:Animals; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C472643:Knl1 protein, human; D008869:Microtubule-Associated Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C432420:SNAP29 protein, human; D050600:SNARE Proteins; C582206:Snap29 protein, Drosophila
keywords: KMN network; SNARE; Snap29; kinetochore; membrane; microtubules; mitosis