title: ASQ2 encodes a TBCC-like protein required for mother-daughter centriole linkage and mitotic spindle orientation.
abstract: An intriguing feature of centrioles is that these highly complicated microtubule-based structures duplicate once per cell cycle, affording the cell precise control over their number. Each cell contains exactly two centrioles, linked together as a pair, one of which is a mother centriole formed in a previous cell cycle and the other of which is a daughter centriole whose assembly is templated by the mother. Neither the molecular basis nor the functional role of mother-daughter centriole linkage is understood. We have identified a mutant, asq2, with defects in centriole linkage. asq2 mutant cells have variable numbers of centrioles and centriole positioning defects. Here, we show that ASQ2 encodes the conserved protein Tbccd1, a member of a protein family including a tubulin folding cochaperone and the retinitis pigmentosa protein RP2, involved in tubulin quality control during ciliogenesis. We characterize mitosis in asq2 cells and show that the majority of cells establish a bipolar spindle but have defects in spindle orientation. Few asq2 cells have centrioles at both poles, and these cells have properly positioned spindles, indicating that centrioles at the poles might be important for spindle orientation. The defects in centriole number control, centriole positioning, and spindle orientation appear to arise from perturbation of centriole linkage mediated by Tbccd1/Asq2p.
authors.affiliation: Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Feldman
authors.forename: Wallace F
authors.initials: WF
authors.lastname: Marshall
mesh_terms: D000818:Animals; D002502:Centrioles / Q000502:physiology*; D016825:Chlamydomonas reinhardtii / Q000502:physiology*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D016254:Mutagenesis, Insertional; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: D008869:Microtubule-Associated Proteins