title: The fission yeast ran GTPase is required for microtubule integrity.
abstract: The microtubule cytoskeleton plays a pivotal role in cytoplasmic organization, cell division, and the correct transmission of genetic information. In a screen designed to identify fission yeast genes required for chromosome segregation, we identified a strain that carries a point mutation in the SpRan GTPase. Ran is an evolutionarily conserved eukaryotic GTPase that directly participates in nucleocytoplasmic transport and whose loss affects many biological processes. Recently a transport-independent effect of Ran on spindle formation in vitro was demonstrated, but the in vivo relevance of these findings was unclear. Here, we report the characterization of a Schizosaccharomyces pombe Ran GTPase partial loss of function mutant in which nucleocytoplasmic protein transport is normal, but the microtubule cytoskeleton is defective, resulting in chromosome missegregation and abnormal cell shape. These abnormalities are exacerbated by microtubule destabilizing drugs, by loss of the spindle checkpoint protein Mph1p, and by mutations in the spindle pole body component Cut11p, indicating that SpRan influences microtubule integrity. As the SpRan mutant phenotype can be partially suppressed by the presence of extra Mal3p, we suggest that SpRan plays a role in microtubule stability.
authors.affiliation: Institut für Mikrobiologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany. fleigu@uni-duesseldorf.de
authors.forename: U
authors.initials: U
authors.lastname: Fleig
authors.forename: S S
authors.initials: SS
authors.lastname: Salus
authors.forename: I
authors.initials: I
authors.lastname: Karig
authors.forename: S
authors.initials: S
authors.lastname: Sazer
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005804:Genes, Lethal / Q000502:physiology; D007399:Interphase / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000201:enzymology*; D008938:Mitosis / Q000502:physiology; D016296:Mutagenesis / Q000502:physiology; D009711:Nucleotides / Q000378:metabolism; D010641:Phenotype; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D008941:Spindle Apparatus / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C103135:Cut1 protein, S pombe; C108851:Mal3 protein, S pombe; D008869:Microtubule-Associated Proteins; D009711:Nucleotides; D029702:Schizosaccharomyces pombe Proteins; D020931:ran GTP-Binding Protein