Dimerization of CPAP Orchestrates Centrosome Cohesion Plasticity

Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China.
Journal of Biological Chemistry (Impact Factor: 4.57). 11/2009; 285(4):2488-97. DOI: 10.1074/jbc.M109.042614
Source: PubMed


Centrosome cohesion and segregation are accurately regulated to prevent an aberrant separation of duplicated centrosomes and to ensure the correct formation of bipolar spindles by a tight coupling with cell cycle machinery. CPAP is a centrosome protein with five coiled-coil domains and plays an important role in the control of brain size in autosomal recessive primary microcephaly. Previous studies showed that CPAP interacts with tubulin and controls centriole length. Here, we reported that CPAP forms a homodimer during interphase, and the fifth coiled-coil domain of CPAP is required for its dimerization. Moreover, this self-interaction is required for maintaining centrosome cohesion and preventing the centrosome from splitting before the G(2)/M phase. Our biochemical studies show that CPAP forms homodimers in vivo. In addition, both monomeric and dimeric CPAP are required for accurate cell division, suggesting that the temporal dynamics of CPAP homodimerization is tightly regulated during the cell cycle. Significantly, our results provide evidence that CPAP is phosphorylated during mitosis, and this phosphorylation releases its intermolecular interaction. Taken together, these results suggest that cell cycle-regulated phosphorylation orchestrates the dynamics of CPAP molecular interaction and centrosome splitting to ensure genomic stability in cell division.

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    • "C-Nap1 (centrosomal Nek2-asso- ciated protein 1) has a role in maintaining this intercentriolar link (and hence the close association of parental centrioles) most likely by acting as the centriolar docking site for rootletin, a major component of the interconnecting fibers (Bahe et al., 2005; Yang et al., 2006). Several other proteins have been implicated in structural or regulatory roles relating to centrosome cohesion, including Cep215, CPAP, dynamin 2, and ␤-catenin (Thompson et al., 2004; Graser et al., 2007b; Bahmanyar et al., 2008; Zhao et al., 2010), suggesting the involvement of multiple mechanisms. However quantitative analysis indicates that C- Nap1 and rootletin are particularly important for the maintenance of centrosome cohesion (Graser et al., 2007b). "
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