Casein Kinase 2 Reverses Tail-Independent Inhibition of Kinesin-1

ORAL

Abstract

Kinesin-1 is a plus-end microtubule-based molecular motor, and defects in kinesin transport are linked to diseases including neurodegeneration. Kinesin can auto-inhibit via a direct head-tail interaction, but is believed to be active otherwise. In contrast, this study uncovers a fast but reversible inhibition distinct from the canonical auto-inhibition pathway. The majority of the initially active kinesin (full-length or tail-less) loses its ability to bind/interact with microtubule, and Casein Kinase 2 (CK2) reverses this inactivation (up to 4-fold) without altering kinesin's single motor properties. Motor phosphorylation is not required for this CK2 -mediated kinesin activation. In cultured mammalian cells, knockdown of CK2 level, but not kinase activity, was sufficient to decrease the force required to stall lipid droplet transport, consistent with a reduction in the number of active motors. We propose that CK2 forms a positive regulating complex with the motor. This study provides the first direct evidence of a protein kinase positively regulating kinesin-transport, and uncovers a pathway whereby inactive cargo-bound kinesin can be activated.

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Authors

  • Jing Xu

    UC Irvine

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara

  • Andreas Bill

    Photonics CoE, Sciprint.org, LLNL, OSU, Imperial College London, General Atomis, UCSD, University of Milan, Instituto Superior Technico, University of Alberta, US Dept. of Agriculture, Agriculture Research Service, Parlier, CA, Dept. of Chemistry, California State University, Fresno, Dept. of Physics, California State University, Fresno, Weizmann Institute of Science, Stanford University, University of Connecticut, Storrs, UC Irvine, University of Missouri-Kansas City, California Institute of Technology, Ulm University, TU Darmstadt, UC Berkeley, GSFC, University of Regenberg, Germany, Lawrence Livermore National Laboratory, Clarendon Laboratory, Oxford, University of California, Los Angeles, Gesellschaft fuer Schwerionenforschung (GSI), Laboratoire pour l'Utilisation des Lasers Intenses, PSFC, MIT, University of California, Santa Barbara, Process Measurements Division, National Institute of Standards and Technology, Gaithersburg, MD, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, Division of Chemistry, California Institute of Technology, Pasadena, CA, Department of Physics, Fars Science and Research Center, Islamic Azad University, Texas A\&M University-Commerce, California State University, Long Beach, Materials Department, University of California Santa Barbara