Fission yeast Pcp1 links polo kinase-mediated mitotic entry to gamma-tubulin-dependent spindle formation.
The centrosomal pericentrin-related proteins play pivotal roles in various aspects of cell division; however their underlying mechanisms remain largely elusive. Here we show that fission-yeast pericentrin-like Pcp1 regulates multiple functions of the spindle pole body (SPB) through recruiting two critical factors, the gamma-tubulin complex (gamma-TuC) and polo kinase (Plo1). We isolated two pcp1 mutants (pcp1-15 and pcp1-18) that display similar abnormal spindles, but with remarkably different molecular defects. Both mutants exhibit defective monopolar spindle microtubules that emanate from the mother SPB. However, while pcp1-15 fails to localise the gamma-TuC to the mitotic SPB, pcp1-18 is specifically defective in recruiting Plo1. Consistently Pcp1 forms a complex with both gamma-TuC and Plo1 in the cell. pcp1-18 is further defective in the mitotic-specific reorganisation of the nuclear envelope (NE), leading to impairment of SPB insertion into the NE. Moreover pcp1-18, but not pcp1-15, is rescued by overproducing nuclear pore components or advancing mitotic onset. The central role for Pcp1 in orchestrating these processes provides mechanistic insight into how the centrosome regulates multiple cellular pathways.
Fong
Chii Shyang
CS
Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
Sato
Masamitsu
M
Toda
Takashi
T
D018797:Cell Cycle Proteins; D018385:Centrosome / Q000378:metabolism; D005800:Genes, Fungal; D007399:Interphase; D046529:Microscopy, Electron, Transmission; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D046912:Multiprotein Complexes; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*
D018797:Cell Cycle Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D014404:Tubulin; C454082:pcp1 protein, S pombe; C501407:Plo1 protein, S pombe; D017346:Protein Serine-Threonine Kinases