Центросома: структура, функции и роль в делении клетки и онкогенезе.

Cell organelle in animal cell helping in cell division

In cell biology, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell cycle progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species. mass of protein termed the pericentriolar material (PCM). The PCM contains proteins responsible for microtubule nucleation and anchoring — including γ tubulin, pericentrin and ninein. In general, each centriole of the centrosome is based on a nine triplet microtubule assembled in a cartwheel structure, and contains centrin, cenexin and tektin. In many cell types, the centrosome is replaced by a cilium during cellular differentiation. However, once the cell starts to divide, the cilium is replaced again by the centrosome.

Centrosomes are associated with the nuclear membrane during the prophase stage of the cell cycle. During mitosis, the nuclear membrane breaks down, and the centrosome nucleated microtubules can interact with the chromosomes to build the mitotic spindle. The mother centriole, the older of the two in the centriole pair, also has a central role in making cilia and flagella. But the processes are essentially different in that centrosome doubling does not occur by template reading and assembly. The mother centriole just aids in the accumulation of materials required for the assembly of the daughter centriole. Centrioles, however, are not required for the progression of mitosis. When the centrioles are irradiated by a laser, mitosis proceeds normally with a morphologically normal spindle. Moreover, development of the fruit fly Drosophila is largely normal when centrioles are absent due to a mutation in a gene required for their duplication. In the absence of the centrioles, the microtubules of the spindle are focused by motors, allowing the formation of a bipolar spindle. Many cells can completely undergo interphase without centrioles.

Theodor Boveri, in 1914, described centrosome aberrations in cancer cells. This initial observation was subsequently extended to many types of human tumors. Centrosome alterations in cancer can be divided in two subgroups — i. e., structural or numeric aberrations — yet both can be found simultaneously in a tumor.

Usually, structural aberrations appear due to uncontrolled expression of centrosome components, or due to post translational modifications (such as phosphorylations) that are not adequate for the components. These modifications may produce variations in centrosome size (usually too large, due to an excess of pericentriolar material). In addition, because centrosomal proteins have a tendency to form aggregates, centrosome related bodies (CRBs) are often observed in ectopic places. Both enlarged centrosomes and CRBs are similar to the centrosomal structures observed in tumors. Even more, these structures can be induced in culture cells by overexpression of specific centrosomal proteins, such as CNap 1 or Nlp. These structures may look very similar, yet detailed studies reveal that they may present very different properties, depending on their proteic composition. For instance, their capacity to incorporate γ TuRC complexes (see also: γ tubulin) can be very variable, and so their capacity to nucleate microtubules However, the method to count the centrosome number (with two centrioles to each centrosome) is often not very precise, because it is frequently assessed using fluorescence microscopy, which does not have high enough optical resolution to resolve centrioles that are very close to each other. Nevertheless, it is clear that the presence of an excess of centrosomes is a common event in human tumors. It has been observed that loss of the tumor suppressor p53 produces superfluous centrosomes, as well as deregulating other proteins implicated in cancer formation in humans, such as BRCA1 and BRCA2. (For references, see

The evolutionary history of the centrosome and the centriole has been traced for some of the signature genes — e. g., the centrins. There exist two main subfamilies of centrins, both of which are present in the early branching eukaryote Giardia intestinalis. Centrins have therefore been present in the common ancestor of eukaryotes. Conversely, they have no recognizable homologs in archea and bacteria and are thus part of the "eukaryotic signature genes". Although there are studies on the evolution of the centrins and centrioles, no studies have been published on the evolution of the pericentriolar material. It is evident that some parts of the centrosome are highly diverged in the model species Drosophila melanogaster and Caenorhabditis elegans. For example, both species have lost one of the centrin subfamilies that are usually associated with centriole duplication. Drosophila melanogaster mutants that lack centrosomes can even develop to morphologically normal adult flies, which then die shortly after birth because their sensory neurons lack cilia. However, subsequent research has shown that centrosome do not contain their own DNA based genomes. While it was confirmed that RNA molecules associate with centrosomes, the sequences have still been found within the nucleus. Furthermore, centrosomes can form de novo after having been removed (e. g., by laser irradiation) from normal cells.