In cell biology, the centrosome is an organelle that serves as the main microtubule organizing
center of the animal cell as well as a regulator of cell-cycle progression.
It was discovered by Edouard Van Beneden in 1883.
and was described and named in 1888 by Theodor Boveri.
The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic
cells.
Fungi and plants lack centrosomes and therefore use other MTOC structures to organize their
microtubules.
Although the centrosome has a key role in efficient mitosis in animal cells, it is not
essential.
Centrosomes are composed of two orthogonally arranged centrioles surrounded by an amorphous
mass of protein termed the pericentriolar material.
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.
Function
Centrosomes are associated with the nuclear membrane during prophase of the cell cycle.
In 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.
The centrosome is copied only once per cell cycle so that each daughter cell inherits
one centrosome, containing two structures called centrioles.
The centrosome replicates during the S phase of the cell cycle.
During the prophase in the process of cell division called mitosis, 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 cancer.
Doubling of a centrosome is similar to DNA replication in two respects: the semiconservative
nature of the process and the action of cdk2 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.
Interestingly, centrioles 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.
Unlike centrioles, centrosomes are required for survival of the organism.
Acentrosomal cells lack radial arrays of astral microtubules.
They are also defective in spindle positioning and in ability to establish a central localization
site in cytokinesis.
The function of centrosome in this context is hypothesized to ensure the fidelity of
cell division 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 C. elegans 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 zygote 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 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, 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 which are not adequate for those
components.
These modifications may produce variations in centrosome size.
On top of this, due to the fact that centrosomal proteins have the tendency to form aggregates,
often centrosome-related bodies 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 can be very variable, and
so their capacity to nucleate microtubules, 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 apparition of genome instability and the loss of tissular
differentiation.
However, the method to count the centrosome number is often not very precise, because
it is frequently assessed using fluorescence microscopy, whose optical resolution is not
high enough to resolve centrioles that are very close to each other.
Nevertheless, it is clear that the presence of supernumerary centrosomes is a common event
in human tumors.
It has been observed that loss of the tumor-suppressor protein p53 produces supernumerary centrosomes,
as well as deregulation of other proteins implicated in tumorigenesis in humans, such
as BRCA1 and BRCA2.
It is important to note that supernumerary centrosomes can be generated by very different
mechanisms: specific reduplication of the centrosome, failure during cell division,
cell fusion 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 would generate a failure in cell division, an increase in ploidy and an increase
in centrosome numbers as a "secondary" effect.
Evolution of the centrosome The evolutionary history of the centrosome
and the centriole has been traced for some of the signature genes, e.g. the centrins.
Centrins participate in calcium signaling and are required for centriole duplication.
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.
Thus, these flies have evolved functionally redundant machinery, which is independent
of the centrosomes.
Centrosome associated nucleotides Research in 2006 indicated that centrosomes
from Surf clam eggs contain RNA sequences.
The sequences identified were found in "few to no" other places in the cell, and do not
appear in existing genome databases.
One identified RNA sequence contains a putative RNA polymerase, 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 from normal cells.
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