title: Suppression of microtubule assembly kinetics by the mitotic protein TPX2.
abstract: TPX2 is a widely conserved microtubule-associated protein that is required for mitotic spindle formation and function. Previous studies have demonstrated that TPX2 is required for the nucleation of microtubules around chromosomes; however, the molecular mechanism by which TPX2 promotes microtubule nucleation remains a mystery. In this study, we found that TPX2 acts to suppress tubulin subunit off-rates during microtubule assembly and disassembly, thus allowing for the support of unprecedentedly slow rates of plus-end microtubule growth, and also leading to a dramatically reduced microtubule shortening rate. These changes in microtubule dynamics can be explained in computational simulations by a moderate increase in tubulin-tubulin bond strength upon TPX2 association with the microtubule lattice, which in turn acts to reduce the departure rate of tubulin subunits from the microtubule ends. Thus, the direct suppression of tubulin subunit off-rates by TPX2 during microtubule growth and shortening could provide a molecular mechanism to explain the nucleation of new microtubules in the presence of TPX2.
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Taylor A
authors: TA
authors: Reid
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Breanna M
authors: BM
authors: Schuster
authors: Department of Biology, University of Massachusetts, Amherst, MA 01003, USA.
authors: Barbara J
authors: BJ
authors: Mann
authors: Department of Biology, University of Massachusetts, Amherst, MA 01003, USA.
authors: Sai Keshavan
authors: SK
authors: Balchand
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Melissa
authors: M
authors: Plooster
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Mark
authors: M
authors: McClellan
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Courtney E
authors: CE
authors: Coombes
authors: Department of Biology, University of Massachusetts, Amherst, MA 01003, USA klei0091@umn.edu patw@bio.umass.edu.
authors: Pat
authors: P
authors: Wadsworth
authors: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA klei0091@umn.edu patw@bio.umass.edu.
authors: Melissa K
authors: MK
authors: Gardner
mesh_terms: D000818:Animals; D002460:Cell Line; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D061987:Sf9 Cells; D008941:Spindle Apparatus / Q000378:metabolism*; D018411:Spodoptera; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D014404:Tubulin
keywords: Dynamic instability; Microtubule; Microtubule-associated protein; Mitosis