title: A Force-Induced Directional Switch of a Molecular Motor Enables Parallel Microtubule Bundle Formation.
abstract: Microtubule-organizing centers (MTOCs) nucleate microtubules that can grow autonomously in any direction. To generate bundles of parallel microtubules originating from a single MTOC, the growth of multiple microtubules needs to coordinated, but the underlying mechanism is unknown. Here, we show that a conserved two-component system consisting of the plus-end tracker EB1 and the minus-end-directed molecular motor Kinesin-14 is sufficient to promote parallel microtubule growth. The underlying mechanism relies on the ability of Kinesin-14 to guide growing plus ends along existing microtubules. The generality of this finding is supported by yeast, Drosophila, and human EB1/Kinesin-14 pairs. We demonstrate that plus-end guiding involves a directional switch of the motor due to a force applied via a growing microtubule end. The described mechanism can account for the generation of parallel microtubule networks required for a broad range of cellular functions such as spindle assembly or cell polarization.
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria; Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria; Research Platform Quantum Phenomena & Nanoscale Biological Systems (QuNaBioS), Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors.forename: Maxim I
authors.initials: MI
authors.lastname: Molodtsov
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Mieck
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Dobbelaere
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dammermann
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria; Department of Molecular Genetics, University of Duisburg-Essen, 45117 Essen, Germany. Electronic address: stefan.westermann@uni-due.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Westermann
authors.affiliation: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria; Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, 1030 Vienna, Austria; Research Platform Quantum Phenomena & Nanoscale Biological Systems (QuNaBioS), Dr. Bohr-Gasse 7, 1030 Vienna, Austria; The Rockefeller University, 1230 York Avenue New York, NY 10065, USA. Electronic address: vaziri@rockefeller.edu.
authors.forename: Alipasha
authors.initials: A
authors.lastname: Vaziri
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D004331:Drosophila melanogaster; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D055595:Mechanical Phenomena; D008868:Microtubule Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C119683:BIM1 protein, S cerevisiae; D018797:Cell Cycle Proteins; C063504:KAR3 protein, S cerevisiae; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D015513:Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; C502598:KIF14 protein, human; C542347:SEN1 protein, S cerevisiae; D004265:DNA Helicases; D020365:RNA Helicases; D016547:Kinesins
keywords: Cik1-Kar3; EB1; Parallel microtubules; directional switch; kinesin-14; microtubule polymerization; plus-end guiding; polarization