title: Alp7/TACC is a crucial target in Ran-GTPase-dependent spindle formation in fission yeast.
abstract: Microtubules are essential intracellular structures involved in several cellular phenomena, including polarity establishment and chromosome segregation. Because the nuclear envelope persists during mitosis (closed mitosis) in fission yeast (Schizosaccharomyces pombe), cytoplasmic microtubules must be reorganized into the spindle in the compartmentalized nucleus on mitotic entry. An ideal mechanism might be to take advantage of an evolutionarily conserved microtubule formation system that uses the Ran-GTPase nuclear transport machinery, but no targets of Ran for spindle formation have been identified in yeast. Here we show that a microtubule-associated protein, Alp7, which forms a complex with Alp14, is a target of Ran in yeast for spindle formation. The Ran-deficient pim1 mutant (pim1-F201S) failed to show mitosis-specific nuclear accumulation of Alp7. Moreover, this mutant exhibited compromised spindle formation and early mitotic delay. Importantly, these defects were suppressed by Alp7 that was artificially targeted to the nucleus by a Ran-independent and importin-alpha-mediated system. Thus, Ran targets Alp7-Alp14 to achieve nuclear spindle formation, and might differentiate its targets depending on whether the organism undergoes closed or open mitosis.
authors.affiliation: Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. masasato@biochem.s.u-tokyo.ac.jp
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D013379:Substrate Specificity; D028901:alpha Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C479626:Alp7 protein, S pombe; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; C432090:alp14 protein, S pombe; D028901:alpha Karyopherins; C490057:pim1 protein, S pombe; D010450:Endopeptidases; C099488:TEV protease; D020931:ran GTP-Binding Protein