title: A non-motor microtubule binding site is essential for the high processivity and mitotic function of kinesin-8 Kif18A.
abstract: BACKGROUND
  Members of the kinesin-8 subfamily are plus end-directed molecular motors that accumulate at the plus-ends of kinetochore-microtubules (kt-MTs) where they regulate MT dynamics. Loss of vertebrate kinesin-8 function induces hyperstable MTs and elongated mitotic spindles accompanied by severe chromosome congression defects. It has been reported that the motility of human kinesin-8, Kif18A, is required for its accumulation at the plus tips of kt-MTs.
  
  
  RESULTS
  Here, we investigate how Kif18A localizes to the plus-ends of kt-MTs. We find that Kif18A lacking its C-terminus does not accumulate on the tips of kt-MTs and fails to fulfill its mitotic function. In vitro studies reveal that Kif18A possesses a non-motor MT binding site located within its C-proximal 121 residues. Using single molecule measurements we find that Kif18A is a highly processive motor and, furthermore, that the C-terminal tail is essential for the high processivity of Kif18A.
  
  
  CONCLUSIONS
  These results show that Kif18A like its yeast orthologue is a highly processive motor. The ability of Kif18A to walk on MTs for a long distance without dissociating depends on a non-motor MT binding site located at the C-terminus of Kif18A. This C-proximal tail of Kif18A is essential for its plus-end accumulation and mitotic function. These findings advance our understanding of how Kif18A accumulates at the tips of kt-MTs to fulfill its function in mitosis.
authors.affiliation: Department of Biology and Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Monika I
authors.initials: MI
authors.lastname: Mayr
authors.forename: Marko
authors.initials: M
authors.lastname: Storch
authors.forename: Jonathon
authors.initials: J
authors.lastname: Howard
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002465:Cell Movement; D045584:Chromosome Positioning; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D015151:Immunoblotting; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D013737:Testis / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C502735:KIF18A protein, human; D016547:Kinesins
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