Fong, C.S. (2010) The role of spindle pole body component Pcp1 in fission yeast. Doctoral thesis, UCL (University College London).
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The centrosomal pericentrin-related proteins play pivotal roles in various aspects of cell division, however their underlying mechanisms have remained largely elusive. Here we show that fission yeast Pcp1, a pericentrin-like protein, regulates multiple functions of the spindle pole body (SPB) by recruiting two crucial factors: γ-tubulin complex (γ-TuC) and polo kinase (Plo1). We isolated two temperature-sensitive pcp1 mutants, pcp1-15 and pcp1-18, that display similar abnormal spindles but with remarkably different molecular defects. pcp1-15 is defective in recruiting γ-TuC to the mitotic SPB, and crucially restoring γ-TuC localisation to the SPB suppresses the mutant. In contrast, pcp1-18 fails to recruit Plo1, which results in defects in mitosis-specific reorganisation of the nuclear envelope (NE) and consequently, impairment of SPB insertion into the NE. Strikingly, pcp1-18 is rescued by overproducing nuclear pore components or advancing mitotic onset. Consistent with these findings, Pcp1 forms a complex with both γ-TuC and Plo1 in the cell. Lastly, we also show that Pcp1 is phosphorylated by Plo1 during mitosis. Our results therefore verify Pcp1’s speculated role in γ-TuC-mediated spindle assembly and unveils its unanticipated function in Plo1-dependent mitotic entry and structural reorganisation of the NE. The central role of Pcp1 in orchestrating multiple SPB functions provides mechanistic insight into how centrosomes regulate multiple cellular pathways, and may be relevant to cancer development due to centrosomal aberrations.
|Title:||The role of spindle pole body component Pcp1 in fission yeast|
|Open access status:||An open access version is available from UCL Discovery|
|Additional information:||The thesis contains the article 'Fission yeast Pcp1 links polo kinase-mediated mitotic entry to γ-tubulin-dependent spindle formation' by Fong, C. S., Sato, M. and Toda, T. (2009) The EMBO Journal, 29, pp. 120 - 130. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.|
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