title: The negatively charged carboxy-terminal tail of β-tubulin promotes proper chromosome segregation.
abstract: Despite the broadly conserved role of microtubules in chromosome segregation, we have a limited understanding of how molecular features of tubulin proteins contribute to the underlying mechanisms. Here we investigate the negatively charged carboxy-terminal tail domains (CTTs) of α- and β-tubulins, using a series of mutants that alter or ablate CTTs in budding yeast. We find that ablating β-CTT causes elevated rates of chromosome loss and cell cycle delay. Complementary live-cell imaging and electron tomography show that β-CTT is necessary to properly position kinetochores and organize microtubules within the assembling spindle. We identify a minimal region of negatively charged amino acids that is necessary and sufficient for proper chromosome segregation and provide evidence that this function may be conserved across species. Our results provide the first in vivo evidence of a specific role for tubulin CTTs in chromosome segregation. We propose that β-CTT promotes the ordered segregation of chromosomes by stabilizing the spindle and contributing to forces that move chromosomes toward the spindle poles.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045.
authors.forename: Colby P
authors.initials: CP
authors.lastname: Fees
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045.
authors.forename: Jayne
authors.initials: J
authors.lastname: Aiken
authors.affiliation: Boulder Laboratory for 3D Electron Microscopy of Cells, University of Colorado Boulder, Boulder, CO 80309.
authors.forename: Eileen T
authors.initials: ET
authors.lastname: O'Toole
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Giddings
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045 jeffrey.moore@ucdenver.edu.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Moore
mesh_terms: D002455:Cell Division; D020090:Chromosome Segregation / Q000502:physiology*; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D000072417:Protein Domains; D004718:Saccharomycetales / Q000235:genetics* / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014404:Tubulin