Subjects
Abstract
Centrosomes are microtubule-organizing centres of animal cells. They influence the morphology of the microtubule cytoskeleton, function as the base for the primary cilium and serve as a nexus for important signalling pathways. At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated pericentriolar material. Cells begin the cell cycle with exactly one centrosome, and the duplication of centrioles is constrained such that it occurs only once per cell cycle and at a specific site in the cell. As a result of this duplication mechanism, the two centrioles differ in age and maturity, and thus have different functions; for example, the older of the two centrioles can initiate the formation of a ciliary axoneme. We discuss spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of centrioles and centrosomes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to the full article PDF.
USD 39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Molecular basis promoting centriole triplet microtubule assembly
Critical constituents and assembly principles of centriole biogenesis in human cells
Architectural basis for cylindrical self-assembly governing Plk4-mediated centriole duplication in human cells
References
Luders, J. & Stearns, T. Microtubule-organizing centres: a re-evaluation. Nat. Rev. Mol. Cell Biol. 8, 161β167 (2007).
Goetz, S. C. & Anderson, K. V. The primary cilium: a signalling centre during vertebrate development. Nat. Rev. Genet. 11, 331β344 (2010).
Carvalho-Santos, Z., Azimzadeh, J., Pereira-Leal, J. B. & Bettencourt-Dias, M. Evolution: Tracing the origins of centrioles, cilia, and flagella. J. Cell Biol. 194, 165β175 (2011).
Nigg, E. A. & Raff, J. W. Centrioles, centrosomes, and cilia in health and disease. Cell 139, 663β678 (2009).
Vaughan, S. & Dawe, H. R. Common themes in centriole and centrosome movements. Trends Cell Biol. 21, 57β66 (2011).
Azimzadeh, J. & Marshall, W. F. Building the centriole. Curr. Biol. 20, R816βR825 (2010).
Bettencourt-Dias, M., Hildebrandt, F., Pellman, D., Woods, G. & Godinho, S. A. Centrosomes and cilia in human disease. Trends Genet. 27, 307β315 (2011).
Avidor-Reiss, T. The cellular and developmental program connecting the centrosome and cilium duplication cycle. Semin. Cell Dev. Biol. 21, 139β141 (2010).
Marshall, W. F. Centriole evolution. Curr. Opin. Cell Biol. 21, 14β19 (2009).
Khodjakov, A. et al. De novo formation of centrosomes in vertebrate cells arrested during S phase. J. Cell Biol. 158, 1171β1181 (2002).
Dammermann, A., Maddox, P. S., Desai, A. & Oegema, K. SAS-4 is recruited to a dynamic structure in newly forming centrioles that is stabilized by the Ξ³-tubulin-mediated addition of centriolar microtubules. J. Cell Biol. 180, 771β785 (2008).
Loncarek, J., Hergert, P., Magidson, V. & Khodjakov, A. Control of daughter centriole formation by the pericentriolar material. Nat. Cell Biol. 10, 322β328 (2008).
Strnad, P. et al. Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle. Dev. Cell 13, 203β213 (2007).
Andersen, J. S. et al. Proteomic characterization of the human centrosome by protein correlation profiling. Nature 426, 570β574 (2003).
Jakobsen, L. et al. Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods. EMBO J. 30, 1520β1535 (2011).
Strnad, P. & Gonczy, P. Mechanisms of procentriole formation. Trends Cell Biol. 18, 389β396 (2008).
Dobbelaere, J. et al. A genome-wide RNAi screen to dissect centriole duplication and centrosome maturation in Drosophila. PLoS Biol. 6, e224 (2008).
Kleylein-Sohn, J. et al. Plk4-induced centriole biogenesis in human cells. Dev. Cell 13, 190β202 (2007).
Rodrigues-Martins, A. et al. DSAS-6 organizes a tube-like centriole precursor, and its absence suggests modularity in centriole assembly. Curr. Biol. 17, 1465β1472 (2007).
Rodrigues-Martins, A., Riparbelli, M., Callaini, G., Glover, D. M. & Bettencourt-Dias, M. Revisiting the role of the mother centriole in centriole biogenesis. Science 316, 1046β1050 (2007).
Peel, N., Stevens, N. R., Basto, R. & Raff, J. W. Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation. Curr. Biol. 17, 834β843 (2007).
Puklowski, A. et al. The SCFβFBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat. Cell Biol. 13, 1004β1009 (2011).
Kitagawa, D., Busso, C., Fluckiger, I. & Gonczy, P. Phosphorylation of SAS-6 by ZYG-1 is critical for centriole formation in C. elegans embryos. Dev. Cell 17, 900β907 (2009).
Bettencourt-Dias, M. et al. SAK/PLK4 is required for centriole duplication and flagella development. Curr. Biol. 15, 2199β2207 (2005).
Habedanck, R., Stierhof, Y. D., Wilkinson, C. J. & Nigg, E. A. The Polo kinase Plk4 functions in centriole duplication. Nat. Cell Biol. 7, 1140β1146 (2005).
Cunha-Ferreira, I. et al. The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr. Biol. 19, 43β49 (2009).
Guderian, G., Westendorf, J., Uldschmid, A. & Nigg, E. A. Plk4 trans-autophosphorylation regulates centriole number by controlling Ξ²TrCP-mediated degradation. J. Cell Sci. 123, 2163β2169 (2010).
Holland, A. J., Lan, W., Niessen, S., Hoover, H. & Cleveland, D. W. Polo-like kinase 4 kinase activity limits centrosome overduplication by autoregulating its own stability. J. Cell Biol. 188, 191β198 (2010).
Rogers, G. C., Rusan, N. M., Roberts, D. M., Peifer, M. & Rogers, S. L. The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J. Cell Biol. 184, 225β239 (2009).
Sillibourne, J. E. et al. Autophosphorylation of polo-like kinase 4 and its role in centriole duplication. Mol. Biol. Cell 21, 547β561 (2010).
Kitagawa, D. et al. PP2A phosphatase acts upon SAS-5 to ensure centriole formation in C. elegans embryos. Dev. Cell 20, 550β562 (2011).
Song, M. H., Liu, Y., Anderson, D. E., Jahng, W. J. & O'Connell, K. F. Protein phosphatase 2A-SUR-6/B55 regulates centriole duplication in C. elegans by controlling the levels of centriole assembly factors. Dev. Cell 20, 563β571 (2011).
Dammermann, A. et al. Centriole assembly requires both centriolar and pericentriolar material proteins. Dev. Cell 7, 815β829 (2004).
Pelletier, L., O'Toole, E., Schwager, A., Hyman, A. A. & Muller-Reichert, T. Centriole assembly in Caenorhabditis elegans. Nature 444, 619β623 (2006).
Nakazawa, Y., Hiraki, M., Kamiya, R. & Hirono, M. SAS-6 is a cartwheel protein that establishes the 9-fold symmetry of the centriole. Curr. Biol. 17, 2169β2174 (2007).
Gopalakrishnan, J. et al. Self-assembling SAS-6 multimer is a core centriole building block. J. Biol. Chem. 285, 8759β8770 (2010).
Stevens, N. R., Dobbelaere, J., Brunk, K., Franz, A. & Raff, J. W. Drosophila Ana2 is a conserved centriole duplication factor. J. Cell Biol. 188, 313β323 (2010).
Kitagawa, D. et al. Structural basis of the 9-fold symmetry of centrioles. Cell 144, 364β375 (2011).
van Breugel, M. et al. Structures of SAS-6 suggest its organization in centrioles. Science 331, 1196β1199 (2011).
Kohlmaier, G. et al. Overly long centrioles and defective cell division upon excess of the SAS-4-related protein CPAP. Curr. Biol. 19, 1012β1018 (2009).
Schmidt, T. I. et al. Control of centriole length by CPAP and CP110. Curr. Biol. 19, 1005β1011 (2009).
Tang, C. J., Fu, R. H., Wu, K. S., Hsu, W. B. & Tang, T. K. CPAP is a cell-cycle regulated protein that controls centriole length. Nat. Cell Biol. 11, 825β831 (2009).
Azimzadeh, J. et al. hPOC5 is a centrin-binding protein required for assembly of full-length centrioles. J. Cell Biol. 185, 101β114 (2009).
Singla, V., Romaguera-Ros, M., Garcia-Verdugo, J. M. & Reiter, J. F. Ofd1, a human disease gene, regulates the length and distal structure of centrioles. Dev. Cell 18, 410β424 (2010).
Spektor, A., Tsang, W. Y., Khoo, D. & Dynlacht, B. D. Cep97 and CP110 suppress a cilia assembly program. Cell 130, 678β690 (2007).
Tsang, W. Y. et al. CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev. Cell 15, 187β197 (2008).
D'Angiolella, V. et al. SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature 466, 138β142 (2010).
Korzeniewski, N., Cuevas, R., Duensing, A. & Duensing, S. Daughter centriole elongation is controlled by proteolysis. Mol. Biol. Cell 21, 3942β3951 (2010).
Bornens, M. Centrosome composition and microtubule anchoring mechanisms. Curr. Opin. Cell Biol. 14, 25β34 (2002).
Cizmecioglu, O. et al. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J. Cell Biol. 191, 731β739 (2010).
Dzhindzhev, N. S. et al. Asterless is a scaffold for the onset of centriole assembly. Nature 467, 714β718 (2010).
Hatch, E. M., Kulukian, A., Holland, A. J., Cleveland, D. W. & Stearns, T. Cep152 interacts with Plk4 and is required for centriole duplication. J. Cell Biol. 191, 721β729 (2010).
Conduit, P. T. et al. Centrioles regulate centrosome size by controlling the rate of Cnn incorporation into the PCM. Curr. Biol. 20, 2178β2186 (2010).
Stevens, N. R., Roque, H. & Raff, J. W. DSas-6 and Ana2 coassemble into tubules to promote centriole duplication and engagement. Dev. Cell 19, 913β919 (2010).
Tsou, M. F. & Stearns, T. Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947β951 (2006).
Tsou, M. F. et al. Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev. Cell 17, 344β354 (2009).
Uhlmann, F., Wernic, D., Poupart, M. A., Koonin, E. V. & Nasmyth, K. Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103, 375β386 (2000).
Nigg, E. A. Centrosome duplication: of rules and licenses. Trends Cell Biol. 17, 215β221 (2007).
SchΓΆckel, L., MΓΆckel, M., Mayer, B., Boos, D. & Stemmann, O. Cleavage of cohesin rings coordinates the separation of centrioles and chromatids. Nat. Cell Biol. 13, 966β972 (2011).
Mayor, T., Stierhof, Y. D., Tanaka, K., Fry, A. M. & Nigg, E. A. The centrosomal protein C-Nap1 is required for cell cycle-regulated centrosome cohesion. J. Cell Biol. 151, 837β846 (2000).
Bahe, S., Stierhof, Y. D., Wilkinson, C. J., Leiss, F. & Nigg, E. A. Rootletin forms centriole-associated filaments and functions in centrosome cohesion. J. Cell Biol. 171, 27β33 (2005).
Yang, J., Adamian, M. & Li, T. Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells. Mol. Biol. Cell 17, 1033β1040 (2006).
Graser, S., Stierhof, Y. D. & Nigg, E. A. Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion. J. Cell Sci. 120, 4321β4331 (2007).
Piel, M., Meyer, P., Khodjakov, A., Rieder, C. L. & Bornens, M. The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317β330 (2000).
Piel, M., Nordberg, J., Euteneuer, U. & Bornens, M. Centrosome-dependent exit of cytokinesis in animal cells. Science 291, 1550β1553 (2001).
Fry, A. M. et al. C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2. J. Cell Biol. 141, 1563β1574 (1998).
Helps, N. R., Luo, X., Barker, H. M. & Cohen, P. T. NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. Biochem. J. 349, 509β518 (2000).
Bertran, M. T. et al. Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J. 30, 2634β2647 (2011).
Mardin, B. R. et al. Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat. Cell Biol. 12, 1166β1176 (2010).
Mardin, B. R., Agircan, F. G., Lange, C. & Schiebel, E. Plk1 Controls the Nek2A-PP1Ξ³ antagonism in centrosome disjunction. Curr. Biol. 21, 1145β1151 (2011).
Halder, G. & Johnson, R. L. Hippo signaling: growth control and beyond. Development 138, 9β22 (2011).
Hergovich, A. et al. The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylation. Curr. Biol. 19, 1692β1702 (2009).
Hardy, P. A. & Zacharias, H. Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors. Cell Biol. Int. 29, 983β992 (2005).
Basto, R. et al. Flies without centrioles. Cell 125, 1375β1386 (2006).
Basto, R. et al. Centrosome amplification can initiate tumorigenesis in flies. Cell 133, 1032β1042 (2008).
Ganem, N. J., Godinho, S. A. & Pellman, D. A mechanism linking extra centrosomes to chromosomal instability. Nature 460, 278β282 (2009).
Silkworth, W. T., Nardi, I. K., Scholl, L. M. & Cimini, D. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PLoS One 4, e6564 (2009).
Kwon, M. et al. Mechanisms to suppress multipolar divisions in cancer cells with extra centrosomes. Genes Dev. 22, 2189β2203 (2008).
Nigg, E. A. Centrosome aberrations: cause or consequence of cancer progression? Nat. Rev. Cancer 2, 815β825 (2002).
Sibon, O. C., Kelkar, A., Lemstra, W. & Theurkauf, W. E. DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos. Nat. Cell Biol. 2, 90β95 (2000).
Hut, H. M. et al. Centrosomes split in the presence of impaired DNA integrity during mitosis. Mol. Biol. Cell 14, 1993β2004 (2003).
Kramer, A. et al. Centrosome-associated Chk1 prevents premature activation of cyclin-BβCdk1 kinase. Nat. Cell Biol. 6, 884β891 (2004).
Matsuyama, M. et al. Nuclear Chk1 prevents premature mitotic entry. J. Cell Sci. 124, 2113β2119 (2011).
Balczon, R. et al. Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells. J. Cell Biol. 130, 105β115 (1995).
Inanc, B., Dodson, H. & Morrison, C. G. A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage. Mol. Biol. Cell 21, 3866β3877 (2010).
Loncarek, J., Hergert, P. & Khodjakov, A. Centriole reduplication during prolonged interphase requires procentriole maturation governed by Plk1. Curr. Biol. 20, 1277β1282 (2010).
Wang, W. J., Soni, R. K., Uryu, K. & Bryan Tsou, M. F. The conversion of centrioles to centrosomes: essential coupling of duplication with segregation. J. Cell Biol. 193, 727β739 (2011).
Hoyer-Fender, S. Centriole maturation and transformation to basal body. Semin. Cell Dev. Biol. 21, 142β147 (2010).
Paintrand, M., Moudjou, M., Delacroix, H. & Bornens, M. Centrosome organization and centriole architecture: their sensitivity to divalent cations. J. Struct. Biol. 108, 107β128 (1992).
Graser, S. et al. Cep164, a novel centriole appendage protein required for primary cilium formation. J. Cell Biol. 179, 321β330 (2007).
Mahjoub, M. R., Xie, Z. & Stearns, T. Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly. J. Cell Biol. 191, 331β346 (2010).
Anderson, C. T. & Stearns, T. Centriole age underlies asynchronous primary cilium growth in mammalian cells. Curr. Biol. 19, 1498β1502 (2009).
Yamashita, Y. M., Jones, D. L. & Fuller, M. T. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301, 1547β1550 (2003).
Rusan, N. M. & Peifer, M. A role for a novel centrosome cycle in asymmetric cell division. J. Cell Biol. 177, 13β20 (2007).
Rebollo, E. et al. Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev. Cell 12, 467β474 (2007).
Januschke, J. & Gonzalez, C. The interphase microtubule aster is a determinant of asymmetric division orientation in Drosophila neuroblasts. J. Cell Biol. 188, 693β706 (2010).
Januschke, J., Llamazares, S., Reina, J. & Gonzalez, C. Drosophila neuroblasts retain the daughter centrosome. Nat. Commun. 2, 243 (2011).
Wang, X. et al. Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461, 947β955 (2009).
Fuentealba, L. C., Eivers, E., Geissert, D., Taelman, V. & De Robertis, E. M. Asymmetric mitosis: Unequal segregation of proteins destined for degradation. Proc. Natl Acad. Sci. USA 105, 7732β7737 (2008).
Lambert, J. D. & Nagy, L. M. Asymmetric inheritance of centrosomally localized mRNAs during embryonic cleavages. Nature 420, 682β686 (2002).
Acknowledgements
We thank the members of the Nigg and Stearns labs for helpful discussion and apologise to our colleagues whose work we were unable to cite for space limitations. E.A.N. was supported by the Swiss National Science Foundation and T.S. was supported by the National Institutes of Health.
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Nigg, E., Stearns, T. The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol 13, 1154β1160 (2011). https://doi.org/10.1038/ncb2345
Published:
Issue date:
DOI: https://doi.org/10.1038/ncb2345
Share this article
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative
This article is cited by
-
Male meiotic spindle poles are stabilized by TACC3 and cKAP5/chTOG differently from female meiotic or somatic mitotic spindles in mice
Scientific Reports (2024)
-
Prolonged overexpression of PLK4 leads to formation of centriole rosette clusters that are connected via canonical centrosome linker proteins
Scientific Reports (2024)
-
Endosulfine alpha maintains spindle pole integrity by recruiting Aurora A during mitosis
BMC Cancer (2023)
-
Cep120 is essential for kidney stromal progenitor cell growth and differentiation
EMBO Reports (2023)
-
A computational spatial whole-Cell model for hepatitis B viral infection and drug interactions
Scientific Reports (2023)
