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CPAP is a cell-cycle regulated protein that controls centriole length

Nature Cell Biology volume 11, pages 825–831 (2009)Cite this article

Abstract

Centriole duplication involves the growing of a procentriole (progeny centriole) next to the proximal end of each pre-existing centriole (parental centriole). The molecular mechanisms that regulate procentriole elongation remain obscure. We show here that expression of the centriolar protein CPAP (centrosomal P4.1-associated protein) is carefully regulated during the cell cycle, with the protein being degraded in late mitosis. Depletion of CPAP inhibited centrosome duplication, whereas excess CPAP induced the formation of elongated procentriole-like structures (PLSs), which contain stable microtubules and several centriolar proteins. Ultrastructural analysis revealed that these structures are similar to procentrioles with elongated microtubules. Overexpression of a CPAP mutant (CPAP-377EE) that does not bind to tubulin dimers significantly inhibited the formation of CPAP-induced PLSs. Together, these results suggest that CPAP is a new regulator of centriole length and its intrinsic tubulin-dimer binding activity is required for procentriole elongation.

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Figure 1: CPAP protein levels are cell-cycle regulated.
Figure 2: Excess CPAP induced the formation of PLSs.
Figure 3: The CPAP-377EE mutant inhibits CPAP-induced PLSs and induces several abnormal mitotic phenotypes.
Figure 4: Depletion of hSAS-6 specifically inhibits the formation of CPAP-induced PLSs derived from procentrioles.
Figure 5: Model showing the role of CPAP in regulating centriole length during centriole biogenesis in human cells.

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Acknowledgements

We thank J. L. Wang and W.-H. Lee for their helpful comments and discussion, and Y.-N. Lin, J.-Y. Shau, Y. Chang, S.-P. Lee, C.-P. Lin and C.-M. Chang for their technical support. This work was supported by a grant from the National Science Council (NSC-97-2321-B-001-011) and from the Institute of Biomedical Science.

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Author notes

  1. Ru-Huei Fu

    Present address: Current address: Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.,

Authors and Affiliations

  1. Institute of Biomedical Sciences, Academia Sinica, 11529, Taipei, Taiwan

    Chieh-Ju C. Tang, Ru-Huei Fu, Kuo-Sheng Wu, Wen-Bin Hsu & Tang K. Tang

  2. Institute of Biochemistry and Molecular Biology, National Yang Ming University, 11221, Taipei, Taiwan

    Kuo-Sheng Wu

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Contributions

C-J. C. T. conducted the experiments and helped with data analysis; R-H. F. and W-B. H. performed the cell-cycle work; K-S.W. assisted with electron microscopy analysis and T.K.T. planned and supervised the project and data analyses.

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Correspondence to Tang K. Tang.

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Tang, CJ., Fu, RH., Wu, KS. et al. CPAP is a cell-cycle regulated protein that controls centriole length. Nat Cell Biol 11, 825–831 (2009). https://doi.org/10.1038/ncb1889

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