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.

Download full-text


Available from: Tomer Avidor-Reiss, Nov 27, 2014
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The centrosome was discovered in the late 19th century when mitosis was first described. Long recognized as a key organelle of the spindle pole, its core component, the centriole, was realized more than 50 or so years later also to comprise the basal body of the cilium. Here, we chart the more recent acquisition of a molecular understanding of centrosome structure and function. The strategies for gaining such knowledge were quickly developed in the yeasts to decipher the structure and function of their distinctive spindle pole bodies. Only within the past decade have studies with model eukaryotes and cultured cells brought a similar degree of sophistication to our understanding of the centrosome duplication cycle and the multiple roles of this organelle and its component parts in cell division and signaling. Now as we begin to understand these functions in the context of development, the way is being opened up for studies of the roles of centrosomes in human disease. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Full-text · Article · Feb 2015 · Cold Spring Harbor Perspectives in Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Centrioles are the key foundation of centrosomes and cilia, yet a molecular understanding of how they form has only recently begun to emerge. Building a fully functional centriole that can form a centrosome and cilium requires two cell cycles. Centriole building starts with procentriole nucleation, a process that is coordinated by the conserved proteins Plk4/Zyg-1, and Asterless/Cep152. Subsequently, Sas-6, a conserved procentriole protein, self-assembles to provide nine-fold symmetry to the centriole scaffold. The procentriole then continues to elongate into a centriole, a process controlled by Sas-4/CPAP and CP110. Then, centrioles recruit Sas-4-mediated pre-assembled centrosomal complexes from the cytoplasm to form the pericentriolar material (PCM). Finally, CP110 and its interacting proteins are involved in controlling the timing of centriole templating of the cilium.
    Full-text · Article · Nov 2012 · Current opinion in cell biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The amount of pericentriolar matrix at the centrosome is tightly linked to both microtubule nucleation and centriole duplication, although the exact mechanism by which pericentriolar matrix levels are regulated is unclear. Here we show that Centrobin, a centrosomal protein, is involved in regulating these levels. Interphase microtubule arrays in Centrobin-depleted cells are more focused around the centrosome and are less stable than the arrays in control cells. Centrobin-depleted cells initiate microtubule nucleation more rapidly than control cells and exhibit an increase in the number of growing microtubule ends emanating from the centrosome, while the parameters of microtubule plus end dynamics around the centrosome are not significantly altered. Finally, we show that Centrobin depletion results in the increased recruitment of pericentriolar matrix proteins to the centrosome, including γ-tubulin, AKAP450, Kendrin and PCM-1. We propose that Centrobin might regulate microtubule nucleation and organization by controlling the amount of pericentriolar matrix.
    Preview · Article · Feb 2013 · Cell cycle (Georgetown, Tex.)
Show more