title: Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8.
abstract: Kinesin-8s are plus-end-directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are "ultraprocessive," a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end-directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of motility. Diffusion is promoted by the tail domain, which also contains a second MT-binding site that decreases the off rate of the motor from the MT lattice. In cells, Kif18B concentrates at the extreme tip of a subset of MTs, superseding EB1. Our data demonstrate that kinesin-8 motors use diverse design principles to target MT plus ends, which likely target them to the plus ends of distinct MT subpopulations in the mitotic spindle.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Yongdae
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232;
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232;
authors.forename: Scott E
authors.initials: SE
authors.lastname: Collier
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232;
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Ohi
authors.affiliation: Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37235 ryoma.ohi@vanderbilt.edu matt.lang@vanderbilt.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lang
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232; ryoma.ohi@vanderbilt.edu matt.lang@vanderbilt.edu.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Ohi
mesh_terms: D055592:Biophysical Phenomena; D058948:Cell Tracking; D004058:Diffusion; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D009038:Motion; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014741:Video Recording
chemical_list: D050505:Mutant Proteins; C552497:KIF18B protein, human; D016547:Kinesins
keywords: EB1; Kif18B; kinesin-8; microtubule; mitosis