title: Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe.
abstract: The size and position of mitotic spindles is determined by the lengths of their constituent microtubules. Regulation of microtubule length requires feedback to set the balance between growth and shrinkage. Whereas negative feedback mechanisms for microtubule length control, based on depolymerizing kinesins and severing proteins, have been studied extensively, positive feedback mechanisms are not known. Here, we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibitor in vitro that uses its processive motor activity as part of a feedback loop to further promote microtubule growth. Positive feedback arises because longer microtubules bind more motors, which walk to the ends where they reinforce growth and inhibit catastrophe. We propose that positive feedback, common in biochemical pathways to switch between signaling states, can also be used in a mechanical signaling pathway to switch between structural states, in this case between short and long polymers.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.|Institute of Biochemistry, ETH Zurich, Zurich, Switzerland.
authors.forename: Anneke
authors.initials: A
authors.lastname: Hibbel
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Aliona
authors.initials: A
authors.lastname: Bogdanova
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, United States.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Mahamdeh
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.|Zentrum für Molekularbiologie der Pflanzen, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Jannasch
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Marko
authors.initials: M
authors.lastname: Storch
authors.affiliation: Zentrum für Molekularbiologie der Pflanzen, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Schäffer
authors.affiliation: CRBM-CRNS, Montpellier, France.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Liakopoulos
authors.affiliation: Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, United States.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Howard
mesh_terms: D025461:Feedback, Physiological; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C075341:KIP2 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: S. cerevisiae; biophysics; cell biology; length regulation; microtubule dynamics; motor protein; positive feedback; structural biology