Centrosome

In, the centrosome (Latin centrum 'center' + Greek sōma 'body') is an that serves as the main  (MTOC) of the animal , as well as a regulator of  progression. The centrosome is thought to have evolved only in the n lineage of. and s lack centrosomes and therefore use structures other than MTOCs to organize their microtubules. Although the centrosome has a key role in efficient in animal cells, it is not essential in certain fly and flatworm species.

Centrosomes are composed of two s arranged at s to each other, and surrounded by an mass of  termed the  (PCM). The PCM contains proteins responsible for and anchoring including,  and. In general, each centriole of the centrosome is based on a nine triplet microtubule assembled in a cartwheel structure, and contains, and. In many cell types the centrosome is replaced by a during  cellular differentiation. However, once the cell starts to divide, the cilium is replaced again by the centrosome.

History
The centrosome was discovered by in 1883, and later described and named in 1888 by.

Functions
Centrosomes are associated with the during the  stage of the cell cycle. In the nuclear membrane breaks down and the centrosome nucleated s can interact with the  to build the.

The mother centriole, the older of the two in the centriole pair, also has a central role in making and.

The centrosome is copied only once per so that each daughter cell inherits one centrosome, containing two structures called centrioles (see also: ). The centrosome replicates during the of the cell cycle. During the in the process of cell division called, the centrosomes migrate to opposite poles of the cell. The mitotic spindle then forms between the two centrosomes. Upon division, each daughter cell receives one centrosome. Aberrant numbers of centrosomes in a cell have been associated with. Doubling of a centrosome is similar to in two respects: the  nature of the process and the action of  as a regulator of the process. 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  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 s allowing the formation of a bipolar spindle. Many cells can completely undergo interphase without centrioles. Unlike centrioles, centrosomes are required for survival of the organism. Cells without centrosomes lack radial arrays of. They are also defective in spindle positioning and in the ability to establish a central localization site in cytokinesis. The function of centrosome in this context is hypothesized to ensure the fidelity of because it greatly increases the efficacy. Some cell types arrest in the following cell cycle when centrosomes are absent. This is not a universal phenomenon.

When the nematode  egg is fertilized the sperm delivers a pair of centrioles. These centrioles will form the centrosomes which will direct the first cell division of the and this will determine its polarity. It's not yet clear whether the role of the centrosome in polarity determination is microtubule dependent or independent.

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

Structural aberrations
Usually they appear due to uncontrolled expression of centrosome components, or due to post-translational modifications (such as phosphorylations) which are not adequate for those components. These modifications may produce variations in centrosome size (usually too big, due to an excess of pericentriolar material). In addition, because centrosomal proteins have the tendency to form aggregates, often centrosome-related bodies (CRBs) are 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: ) can be very variable, and so their capacity to nucleate s, therefore affecting in different way the shape, polarity and motility of implicated tumor cells.

Numeric aberrations
The presence of an inadequate number of centrosomes is very often linked to the appearance of and the loss of tissue differentiation. However, the method to count the centrosome number (each one with 2 centrioles) is often not very precise, because it is frequently assessed using, whose is not high enough 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 produces superfluous centrosomes, as well as deregulating other proteins implicated in  formation in humans, such as  and  (for references, see ). An excess of centrosomes can be generated by very different mechanisms: specific reduplication of the centrosome, cytokinesis failure during (generating an increase in chromosome number), cell fusion (for instance due to infection by specific viruses) or de novo generation of centrosomes. At this point there is not sufficient information to know how frequent are those mechanisms in vivo, but it is possible that the increase in centrosome numbers due to a failure during cell division might be more frequent than appreciated, because many "primary" defects in one cell (deregulation of the, defective or  metabolism, failure in the , etc...) would generate a failure in cell division, an increase in  and an increase in centrosome numbers as a "secondary" effect.

Evolution
The ary history of the centrosome and the has been traced for some of the signature genes, e.g. the. Centrins participate in and are required for centriole duplication. There exist two main subfamilies of centrins, both of which are present in the early-branching . Centrins have therefore been present in the common ancestor of eukaryotes. Conversely, they have no recognizable s in and  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.

It is evident that some parts of the centrosome are highly diverged in the model species ' and '. 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. Thus, these flies have evolved functionally redundant machinery, which is independent of the centrosomes.

Associated nucleotides
Research in 2006 indicated that centrosomes from eggs contain. The sequences identified were found in "few to no" other places in the cell, and do not appear in existing databases. One identified RNA sequence contains a putative, leading to the hypothesis of an RNA based genome within the centrosome. 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.