The absence of a centrosome in Planaria provides food for thought. In planarians, centrosomes are never found at the poles of the spindle [ 20 ]. Centrioles are only present in epithelial cells, where they are assembled de novo and build motile cilia after anchoring at the cell membrane. Remarkably, Planaria lost from its genome several genes that are known to be involved in forming a centrosome; that is, in endowing the centriole with the ability to nucleate microtubules [ 20 ].
A consequence of their depletion is that cells inherit abnormal centriole numbers [ 23 , 30 , 31 ]. Furthermore, it is known that NEK2 is involved in centrosome separation, a process that is necessary for centrosomes to localize to opposite spindle poles at the entry to mitosis [ 32 ].
The above arguments suggest that the localization of centrioles at or close to spindle poles via direct microtubule nucleation or through binding to a MTOC is likely to be a strategy to ensure equal inheritance of these structures. However, given that the centrosome plays important roles in cell division in several organisms and tissue types, it is possible that it has been co-opted to actively participate in spindle assembly in certain contexts [ 18 ].
Different cells have different numbers of centrioles. While, as discussed above, most oocytes have no centrioles, in mammalian epithelial multiciliated cells, such as the ones of the vertebrate respiratory system, to basal bodies are formed in each cell after differentiation.
Multiple centrioles form around a mother centriole, differing from the usual pattern of one daughter centriole per mother centriole. Centrioles can also form around less characterized, non-microtubule-based dense structures of heterogeneous size, called deuterosomes, whose composition is unknown reviewed in [ 4 , 16 , 22 ] Figure 3 b.
In a dividing cell the number of centrosomes is highly controlled through a canonical duplication cycle in coordination with the chromosome cycle Figure 3 a : one centriole forms per mother centriole in each cell cycle.
Four structural steps were defined through electron microscopy in the canonical cycle: separation called disengagement of the centrioles, formation of the daughter centrioles close to the mother, elongation of the daughters and separation of the centrosomes in G2 reviewed in [ 5 , 6 , 9 ]; Figure 3 a. While a cell in G1 has one centrosome, during the rest of interphase and mitosis it has two, with each centrosome harboring two visible centrioles from S phase.
In G2 the two centrosomes separate and their presence as individual entities becomes more obvious. Thus, when the cell enters mitosis it is equipped with two centrosomes, each with two centrioles, which participate in mitotic spindle assembly. The centriole cycle is regulated by the same machinery that regulates the chromosome cycle, such as cyclin-dependent kinases Figure 3 a.
How those molecules regulate centriole components is not known reviewed in [ 5 , 6 ]. Several remarkable rules regulate centriole number and localization in canonical centrosome biogenesis: it occurs once per cell cycle, only one daughter is formed per mother, and no centrioles are formed away from the mother.
Once centrioles have duplicated in S phase, they cannot duplicate again until the next S phase. Disengagement of the centrioles at the exit of mitosis is a prerequisite for duplication in the next cell cycle and much work is now focused on understanding this step.
Little is known about the control that ensures that one and only one daughter centriole forms close to each mother. Centrioles can also appear without a pre-existing centriole de novo formation. De novo biogenesis is known to occur in insect species with parthenogenic development, as well as in human cells upon laser ablation of their centrosomes or overexpressing some centriole regulators Figure 3 c.
The localization and number of these centrioles is not determined and can change significantly. Clearly the de novo pathway is regulated by the same molecules as the canonical pathway, however it has to be very well controlled to avoid multiple centriole formation in normal cells [ 5 , 6 , 9 ].
Centriole age, and in consequence centrosome age, might be physiologically and developmentally very important. A consequence of the centriole cycle is that each centrosome in a mitotic cell has a different age: one has a mother and a daughter, the other a grandmother and a daughter centriole. These differences provide variation in the competence for PCM acquisition, microtubule nucleation, anchoring and cilia formation.
After cytokinesis the cell inheriting the grandmother, appendage-harboring centriole, grows the primary cilia first and is thus able to respond to signaling cues, which may generate asymmetry amongst those cells [ 33 , 34 ]. This topic deserves more attention, as a recent study has shown that randomization of centrosome inheritance does not affect asymmetric cell division [ 37 ].
How the age of a centriole affects its ability to be retained in one cell versus another is a very interesting question. One possibility is that centriole microtubule-nucleating and microtubule-anchoring capacity defines the population of astral microtubules associated with that centrosome and this may provide different connections with the cell cortex. Indeed, the age of the centriole determines the presence of particular proteins at each centriole, which then determines their specific microtubule nucleating capacity and centrosome inheritance [ 37 ].
A variety of human diseases have been linked to centrioles and centrosomes, such as diseases of brain development, cancer and ciliopathies.
The most common phenotypes in brain disorders associated with those proteins are generalized disorders of growth where the brain is disproportionately affected; and the primary microcephalies where the brain alone is affected and significantly reduced in size.
One current hypothesis for the latter is that centrosomes help in spindle positioning in neural progenitors, contributing to a balance between expansion of progenitors and generation of neurons. It is equally possible that some of the divisions with abnormal centrosomes might lead to aneuploidy and cell death. Animal models of the human mutations associated with those diseases should play an important role in the understanding of their genesis reviewed in [ 38 , 39 ].
With respect to cancer, Boveri, Hansemann and Galeotti, more than a century ago, proposed that abnormalities in centriole duplication could be at the origin of the genome instability observed in cancer cells [ 39 , 40 ]. Centrosome abnormalities can occur early in pre-malignant lesions and are extensively correlated with aneuploidy, supporting a direct role for extra centrosomes in tumorigenesis [ 40 ]. Moreover, the presence of abnormally high numbers of centrosomes per cell can generate tumors in flies [ 41 ].
How can abnormally high numbers of centrosomes generate cancer? Cancer cells adapt to dividing in the presence of supernumerary centrosomes by clustering them at the poles of a bipolar spindle; however, in the process of organizing a bipolar spindle those cells may generate abnormal chromatid attachments that lead to aneuploidy reviewed in [ 39 , 42 ]. Extra centrosomes can also interfere with asymmetric cell divisions, which may lead to hyperproliferation [ 41 ] reviewed in [ 39 ]. Supernumerary centrioles may also generate supernumerary cilia, which lead to abnormal ciliary signaling for example, hedgehog , at least in tissue culture cells [ 33 ].
What about ciliopathies? Cilia can be motile or immotile, such as those of specialized cells like photoreceptors, and of primary cilia, which are sensing structures that exist in most human cells. Motile cilia assembly defects were first associated with bronchitis, sinusitis, and sperm immotility. Changes in body symmetry have shown that ciliary motility is essential to create directional flow in the early embryo, initiating the normal left-right developmental program.
This is the case of several rare disorders, such as polycystic kidney disease, nephronophthisis, retinitis pigmentosa, and Bardet-Biedl, Joubert and Meckel syndromes. The study of those proteins is contributing to a better understanding of the function of immotile cilia. In particular, in several of those diseases the microtubule-based structure of the cilia is not altered, while its sensory function might be [ 39 , 43 ].
Bornens M: The centrosome in cells and organisms. Nat Cell Biol. Curr Opin Cell Biol. Nat Rev Mol Cell Biol. Article PubMed Google Scholar. EMBO J. Fu J, Glover DM: Structured illumination of the interface between centriole and peri-centriolar material. Open Biol.
Nat Commun. Biol Open. Curr Biol. Cell Mol Life Sci. Mol Biol Cell. J Cell Biol. Sluder, G. The good, the bad and the ugly: the practical consequences of centrosome amplification.
Cell Biol. Badano, J. The centrosome in human genetic disease. Praetorius, H. A physiological view of the primary cilium. Kuriyama, R. Centriole cycle in Chinese hamster ovary cells as determined by whole-mount electron microscopy. Robbins, E. The centriole cycle in synchronized HeLa cells. Google Scholar. Kochanski, R. Mode of centriole duplication and distribution. Alvey, P. An investigation of the centriole cycle using 3T3 and CHO cells.
Cell Sci. Vorobjev, I. Centrioles in the cell cycle. Epithelial cells. Blow, J. Preventing re-replication of chromosomal DNA.
Machida, Y. Right place, right time, and only once: replication initiation in metazoans. Cell , 13—24 La Terra, S. Defines the properties of de novo assembled centrioles in HeLa cells: they are born in S phase; they mature in the next cycle; and the presence of a single centriole inhibits the assembly of additional centrioles.
Marshall, W. Kinetics and regulation of de novo centriole assembly. Implications for the mechanism of centriole duplication. Defines the properties of de novo assembled centrioles in C. The presence of a single centriole inhibits the assembly of additional centrioles, and the rate of de novo assembly is approximately half the rate of templated duplication. Riparbelli, M. Drosophila parthenogenesis: a model for de novo centrosome assembly. Andersen, J.
Proteomic characterization of the human centrosome by protein correlation profiling. Nature , — Ostrowski, L. A proteomic analysis of human cilia: identification of novel components. Proteomics 1 , — Keller, L. Proteomic analysis of isolated Chlamydomonas centrioles reveals orthologs of ciliary-disease genes. Pazour, G. Proteomic analysis of a eukaryotic cilium. Stolc, V. Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes.
Natl Acad. USA , — Li, J. Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell , — References 21 and 22 use comparative genomics to predict the ciliary and basal body proteomes, leading to a global evolutionary view and to human disease-gene candidates. Avidor-Reiss, T. Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis.
Leidel, S. Centrosome duplication and nematodes: recent insights from an old relationship. Cell 9 , — SAS-6 defines a protein family required for centrosome duplication in C. Nature Cell Biol. Identification and characterization of SAS-6, a conserved regulator of centriole biogenesis, the overexpression of which leads to the amplification of MTOCs.
SAS-4 is essential for centrosome duplication in C. Cell 4 , — Gonczy, P. Functional genomic analysis of cell division in C. Pelletier, L. The Caenorhabditis elegans centrosomal protein SPD-2 is required for both pericentriolar material recruitment and centriole duplication.
Dammermann, A. Centriole assembly requires both centriolar and pericentriolar material proteins. Cell 7 , — Identification and characterization of SAS-6, a conserved regulator of centriole biogenesis. Bettencourt-Dias, M. Both references 29 and 36 show that cells without centrioles can proliferate in the context of a whole organism.
However, centrioles are needed to form basal bodies and for male meiotic divisions. Habedanck, R. The Polo kinase Plk4 functions in centriole duplication. Genome-wide survey of protein kinases required for cell cycle progression.
Paintrand, M. Centrosome organization and centriole architecture: their sensitivity to divalent cations. Bornens, M. Centrosome composition and microtubule anchoring mechanisms. Centriole number and the reproductive capacity of spindle poles.
Kirkham, M. SAS-4 is a C. Basto, R. Flies without centrioles. See also reference The authors also show that asymmetrical cell division can occur without centrioles although not always. Bobinnec, Y. Centriole disassembly in vivo and its effect on centrosome structure and function in vertebrate cells.
Reproductive capacity of sea urchin centrosomes without centrioles. Cell Motil. Cytoskeleton 13 , — Janke, C. Tubulin polyglutamylase enzymes are members of the TTL domain protein family.
Science , — Hinchcliffe, E. Two proteins isolated from sea urchin sperm flagella: structural components common to the stable microtubules of axonemes and centrioles. Steffen, W. Evidence for tektins in centrioles and axonemal microtubules. USA 85 , — Azimzadeh, J. Blagden, S. Polar expeditions — provisioning the centrosome for mitosis. Zheng, Y. Verollet, C. Sawin, K.
Cytoplasmic microtubule organization in fission yeast. Yeast 23 , — Delgehyr, N. Microtubule nucleation and anchoring at the centrosome are independent processes linked by ninein function. Bartolini, F. Generation of noncentrosomal microtubule arrays. Doxsey, S. Re-evaluating centrosome function.
Trinkle-Mulcahy, L. Mitotic phosphatases: no longer silent partners. Glover, D. Polo kinase and progression through M phase in Drosophila : a perspective from the spindle poles. Oncogene 24 , — Giet, R. Barros, T. Peset, I. Brittle, A. EMBO J. Sankaran, S. Identification of domains of BRCA1 critical for the ubiquitin-dependent inhibition of centrosome function.
Cancer Res. Kemp, C. Centrosome maturation and duplication in C. Cell 6 , — Dutcher, S. Rieder, C. The resorption of primary cilia during mitosis in a vertebrate PtK1 cell line. Ishikawa, H. The authors deleted both alleles of the Odf2 gene in mouse F9 cells and found that Odf2 is indispensable for the formation of distal and subdistal appendages and the generation of primary cilia, providing evidence for the direct involvement of appendages in cilia formation.
Centrosomes in cellular regulation. Cell Dev. Two-way traffic: centrosomes and the cell cycle. Centrosome control of the cell cycle. Trends Cell Biol. Piel, M. The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. Shows that only the maternal centriole retains, and presumably anchors, microtubules. Also shows that daughter centrioles are dynamic and that their movements are coordinated with those of the mother centriole, which suggests a molecular link between them.
Centrosome-dependent exit of cytokinesis in animal cells. References 66—68 show that somatic cells can form a spindle in the absence of centrosomes but show defects in cytokinesis and S phase progression. Khodjakov, A. Centrosomes enhance the fidelity of cytokinesis in vertebrates and are required for cell cycle progression.
Requirement of a centrosomal activity for cell cycle progression through G1 into S phase. Krapp, A. SIN and the art of splitting the fission yeast cell. Seshan, A. Linked for life: temporal and spatial coordination of late mitotic events.
Magidson, V. Before cell division, the centrosome duplicates and then, as division begins, the two centrosomes move to opposite ends of the cell.
Proteins called microtubules assemble into a spindle between the two centrosomes and help separate the replicated chromosomes into the daughter cells. The centrosome is an important part of how the cell organizes the cell division. There are a lot of processes that need to be coordinated together when you have two cells, both their nucleus and the cytoplasm, moving away from each other.
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