Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature Cell Biology (Impact Factor: 19.68). 06/2012; 14(8):865-73. DOI: 10.1038/ncb2527
Source: PubMed


Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM). PCM assembly is a tightly regulated, critical step that determines the size and capability of centrosomes. Here, we report a role for tubulin in regulating PCM recruitment through the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins. A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These results suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, the regulation of PCM recruitment by tubulin depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules. On the basis of its guanine-bound state, tubulin can act as a molecular switch in PCM recruitment.

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Available from: Tomer Avidor-Reiss, Nov 27, 2014
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    • "This reflects the ability of Sas-4 to form complexes with CNN and Dplp; centrosomes with mutant Sas-4 unable to form such complexes have reduced PCM (Dzhindzhev et al. 2010; Gopalakrishnan et al. 2011). A double mutation in Sas-4 protein sequence that abolishes its binding to tubulin enhances centrosomal protein complex formation leading to abnormally large centrosomes and asters (Gopalakrishnan et al. 2012). Thus, tubulin binding may interfere with Sas-4-mediated PCM assembly. "
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