title: A tethering mechanism controls the processivity and kinetochore-microtubule plus-end enrichment of the kinesin-8 Kif18A.
abstract: Metaphase chromosome positioning depends on Kif18A, a kinesin-8 that accumulates at and suppresses the dynamics of K-MT plus ends. By engineering Kif18A mutants that suppress MT dynamics but fail to concentrate at K-MT plus ends, we identify a mechanism that allows Kif18A to accumulate at K-MT plus ends to a level required to suppress chromosome movements. Enrichment of Kif18A at K-MT plus ends depends on its C-terminal tail domain, while the ability of Kif18A to suppress MT growth is conferred by the N-terminal motor domain. The Kif18A tail contains a second MT-binding domain that diffuses along the MT lattice, suggesting that it tethers the motor to the MT track. Consistently, the tail enhances Kif18A processivity and is crucial for it to accumulate at K-MT plus ends. The heightened processivity of Kif18A, conferred by its tail domain, thus promotes concentration of Kif18A at K-MT plus ends, where it suppresses their dynamics to control chromosome movements.
authors: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Jason
authors: J
authors: Stumpff
authors: Yaqing
authors: Y
authors: Du
authors: Chauca A
authors: CA
authors: English
authors: Zoltan
authors: Z
authors: Maliga
authors: Michael
authors: M
authors: Wagenbach
authors: Charles L
authors: CL
authors: Asbury
authors: Linda
authors: L
authors: Wordeman
authors: Ryoma
authors: R
authors: Ohi
mesh_terms: D045584:Chromosome Positioning; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*
chemical_list: C502735:KIF18A protein, human; D016547:Kinesins