The center (∼1 µm) where spindle fibers (microtubules) originate (a microtubule organizing center, MTOC) and develop from a pair of centrioles toward the centromeres during nuclear divisions in animals (and few lower plants). In normal mammalian cells there are two centrosomes at the opposite poles (see Fig. C57). The mother centrosome normally remains anchored to the hub of the Drosophila germ stem cell interface and is inherited by the stem cell, whereas the daughter centrosome moves away from the hub and is inherited by the cell that commits to differentiation (Yamashita YM et al 2007 Science 315:518). In the human mammary epithelial cells there may be split centrosomes as an anomaly. Loss of p16INK4a causes splitting of the centriole that can lead to the formation of aneuploidy and genomic instability because multipolar mitoses may take place. Normally, p16INK4a in cooperation with p21 regulate cyclin-dependent kinases and prevent the splitting of the centriole. Such a condition may lead to tumorigenesis. In the mammalian female, meiosis centrosomes are lacking and the chromosomes nucleate and stabilize the bipolar spindle. This task is performed by the chromosomal passenger complex containing the Dasra A and B proteins, INCENP (inner centromere protein), Survivin, and the Aurora kinase (Sampath SC et al 2004 Cell 118:187). Ubiquitination and deubiquitination enzymes are required for the association and dissociation of Survivin to the centromeres for chromosome alignment and segregation (Vong QP et al 2005 Science 310:1499). In case the spindle emanates from the centrioles, Ran DTPase releases factors from a pool sequestered by β-importin required for activation of spindle assembly. A pericentriolar material made of γ-tubulin and Asp (asymmetric spindle) protein of 220 kDa surrounds the centrioles. The γ-globulin ring complex (γ-Turc) can fulfill its function even when it is outside the centrosome (Müller H et al 2006 Science 314:654). Asp has phosphorylation sites for p34 and other mitogen-activated kinases as well as binding domains for actin and calmodulin. The fast growing (plus) ends of the microtubules project into the cytoplasm whereas the slow-growing (minus) ends are embedded into the γ-globulin ring. MAPs (microtubule-associated proteins) are also required for the nucleation at the centrosomes. The division of the centrosome (also called centrosome cycle) is essential for the completion of the cell cycle in animals and it may be blocked by mutation in gene cdc31. For the initiation of the division of the centrosome in Xenopus, egg calcium, calmodulin and calcium/calmodulin-dependent protein kinase II are required (Matsumoto Y, Maller JL 2002 Science 295:499). The aurora-2/STK15 serine/threonine kinase (encoded in human chromosome 20q13.2) is associated with the centrosome and its amplification interferes with the normal function of the centromere resulting in aneuploidy in common cancer cells. The PML protein also regulates centrosome duplication by suppression of the Aurora protein (Xu Z-X et al 2005 Mol Cell 17:721). CDK2-cyclin E may cause abnormally high proliferation of the centrosomes as it phosphorylates nucleophosmin, a centrosomal protein. Hsp90 is also a component of the centrosomal core, along with several other proteins. The deficiency of the p53 tumor suppressor protein results in multiple centrosomes and unequal distribution of chromosomes. Similar are the consequences of defects in PLK1 and an ataxia telangiectasia (rad3)-related (ATR) mutation. Plants do not have such distinct structures. Recently, mutations affecting the centrosomes have been isolated. The centrosome is paternally derived during fertilization in the majority of the animal species. Depending on the sperm donor, the size of the aster may vary. The centrosome is required also for DNA synthesis during the cell cycle. Defect of centrosomes may lead to aneuploidy and cancer and centrosome anomalies contribute to several human diseases (Badano JL et al 2005 Nature Rev Genet 6:194). mitosis, centrioles, p16INK4 , p21, centromere, spindle, microtubule, nucleation, kinesis, dynein, importin, Ran, spindle pole body, aster, centrosomin, multipolar spindle, Cdk; p34, actin, calmodulin, P53, Hsp90, aneuploidy, survivin; Aurora, promyelocytic leukemia; Brinkley BR 2001 Trends Cell Biol 11:18; Stearns T 2001 Cell 105:417; Bornens M, Piel M 2001 Curr Biol 12:R71; Bornens M 2002 Current Opin Cell Biol 14:25; Meraldi P, Nigg EA 2002 FEBS Lett 521:9; Andersen JS et al 2003 Nature [Lond] 425:570; centrosome–centriole duplication: Leidel S, Gönczy P 2005 Developmental Cell 9:317.
© Springer Science+Business Media 2008
Reference Work Entry Metrics
- Reference Work Title
- Encyclopedia of Genetics, Genomics, Proteomics and Informatics
- pp 313-314
- Print ISBN
- Online ISBN
- Springer Netherlands
- Copyright Holder
- Springer Science+Business Media
- Additional Links
- Industry Sectors
- eBook Packages
To view the rest of this content please follow the download PDF link above.