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In
cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
, the centrosome (Latin centrum 'center' + Greek sōma 'body') (archaically cytocentre) is an
organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
that serves as the main
microtubule organizing center The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spind ...
(MTOC) of the animal
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
, as well as a regulator of
cell-cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subse ...
progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the
metazoa Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
n lineage of
eukaryotic cells Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the ...
.
Fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
and
plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
s lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
in animal cells, it is not essential in certain fly and flatworm species. Centrosomes are composed of two
centriole In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers (Pinophyta), flowering plants (angiosperms) and most fungi, and a ...
s arranged at
right angle In geometry and trigonometry, a right angle is an angle of exactly 90 Degree (angle), degrees or radians corresponding to a quarter turn (geometry), turn. If a Line (mathematics)#Ray, ray is placed so that its endpoint is on a line and the ad ...
s to each other, and surrounded by a dense, highly structured mass of
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
termed the
pericentriolar material Pericentriolar material (PCM, sometimes also called pericent matrix) is a highly structured, dense mass of protein which makes up the part of the animal centrosome that surrounds the two centrioles. The PCM contains proteins responsible for microtub ...
(PCM). The PCM contains proteins responsible for
microtubule nucleation In cell biology, microtubule nucleation is the event that initiates '' de novo'' formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of t ...
and anchoring — including
γ-tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
,
pericentrin Pericentrin (kendrin), also known as PCNT and pericentrin-B (PCNTB), is a protein which in humans is encoded by the ''PCNT'' gene on chromosome 21. This protein localizes to the centrosome and recruits proteins to the pericentriolar matrix (PCM) ...
and
ninein Ninein is a protein that in humans is encoded by the ''NIN'' gene. Ninein, together with its paralog Ninein-like protein is one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the micr ...
. In general, each centriole of the centrosome is based on a nine-triplet microtubule assembled in a cartwheel structure, and contains
centrin Centrins, also known as caltractins, are a family of calcium-binding phosphoproteins found in the centrosome of eukaryotes. Centrins are present in the centrioles and pericentriolar lattice. Human centrin genes are CETN1, CETN2 and CETN3. Hist ...
,
cenexin Outer dense fiber protein 2, also known as cenexin, is a protein that in humans is encoded by the ''ODF2'' gene. The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm t ...
and
tektin Tektins are cytoskeletal proteins found in cilia and flagella as structural components of outer doublet microtubules. They are also present in centrioles and basal bodies. They are polymeric in nature, and form filaments.MA Pirner and RW Linck ...
. In many cell types, the centrosome is replaced by a
cilium The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
during cellular differentiation. However, once the cell starts to divide, the cilium is replaced again by the centrosome.


History

The centrosome was discovered jointly by
Walther Flemming Walther Flemming (21 April 1843 – 4 August 1905) was a German biologist and a founder of cytogenetics. He was born in Sachsenberg (now part of Schwerin) as the fifth child and only son of the psychiatrist Carl Friedrich Flemming (1799–18 ...
in 1875 and Edouard Van Beneden in 1876, and later described and named in 1888 by
Theodor Boveri Theodor Heinrich Boveri (12 October 1862 – 15 October 1915) was a German zoologist, comparative anatomist and co-founder of modern cytology. He was notable for the first hypothesis regarding cellular processes that cause cancer, and for descr ...
.


Functions

Centrosomes are associated with the
nuclear membrane The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membrane ...
during the
prophase Prophase () is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin retic ...
stage of the cell cycle. During
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
, the nuclear membrane breaks down, and the centrosome-nucleated
microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
s can interact with the
chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
to build the
mitotic spindle In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...
. The mother centriole, the older of the two in the centriole pair, also has a central role in making
cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
and
flagella A flagellum (; ) is a hairlike appendage that protrudes from certain plant and animal sperm cells, and from a wide range of microorganisms to provide motility. Many protists with flagella are termed as flagellates. A microorganism may have f ...
. The centrosome is copied only once per
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
, so that each daughter cell inherits one centrosome, containing two structures called centrioles. The centrosome replicates during the
S phase S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...
of the cell cycle. During the
prophase Prophase () is the first stage of cell division in both mitosis and meiosis. Beginning after interphase, DNA has already been replicated when the cell enters prophase. The main occurrences in prophase are the condensation of the chromatin retic ...
in the process of cell division called
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
, 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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. Doubling of a centrosome is similar to
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
in two respects: the semiconservative nature of the process and the action of
CDK2 Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ''CDK2'' gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein ...
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 ''
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' 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
motor An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power g ...
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
astral microtubules An aster is a cellular structure shaped like a star, consisting of a centrosome and its associated microtubules during the early stages of mitosis in an animal cell. Asters do not form during mitosis in plants. Astral rays, composed of microtub ...
. They are also defective in spindle positioning and in the ability to establish a central localization site in cytokinesis. The function of centrosomes in this context is hypothesized to ensure the fidelity of
cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
, 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 ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'' 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 A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicellula ...
, 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. In human reproduction, the
sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
supplies the centriole that creates the centrosome and microtubule system of the zygote.


Centrosome alterations in cancer cells

Theodor Boveri Theodor Heinrich Boveri (12 October 1862 – 15 October 1915) was a German zoologist, comparative anatomist and co-founder of modern cytology. He was notable for the first hypothesis regarding cellular processes that cause cancer, and for descr ...
, in 1914, described centrosome aberrations in
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
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.


Structural aberrations

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 Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ...
) can be very variable, and so their capacity to nucleate
microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 an ...
s therefore affects the shape, polarity and motility of implicated tumor cells in different ways.


Numeric aberrations

The presence of an inadequate number of centrosomes is very often linked to the appearance of
genome instability Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneup ...
and the loss of tissue differentiation. 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 A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. "Fluorescence microscop ...
, which does not have high enough
optical resolution Optical resolution describes the ability of an imaging system to resolve detail, in the object that is being imaged. An imaging system may have many individual components, including one or more lenses, and/or recording and display components. ...
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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
formation in humans, such as
BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
and
BRCA2 ''BRCA2'' and BRCA2 () are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) ...
. (For references, see .) An excess of centrosomes can be generated by very different mechanisms: specific reduplication of the centrosome, cytokinesis failure during
cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
(generating an increase in chromosome number), cell fusion (such as in cases of infection by specific viruses) or ''de novo'' generation of centrosomes. At this point, there is insufficient information to know how prevalent these mechanisms are ''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
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
, defective DNA or
chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
metabolism, failure in the
spindle checkpoint The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during mitosis or meiosis that prevents the separa ...
, etc.) would generate a failure in cell division, an increase in
ploidy Ploidy () is the number of complete sets of chromosomes in a cell (biology), cell, and hence the number of possible alleles for Autosome, autosomal and Pseudoautosomal region, pseudoautosomal genes. Sets of chromosomes refer to the number of mat ...
and an increase in centrosome numbers as a "secondary" effect.


Evolution

The
evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
ary history of the centrosome and the
centriole In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers (Pinophyta), flowering plants (angiosperms) and most fungi, and a ...
has been traced for some of the signature genes — e.g., the
centrins Centrins, also known as caltractins, are a family of calcium-binding phosphoproteins found in the centrosome of eukaryotes. Centrins are present in the centrioles and pericentriolar lattice. Human centrin genes are CETN1, CETN2 and CETN3. History ...
. Centrins participate in
calcium signaling Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allos ...
and are required for centriole duplication. There exist two main subfamilies of centrins, both of which are present in the early-branching
eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
''
Giardia intestinalis ''Giardia duodenalis'', also known as ''Giardia intestinalis'' and ''Giardia lamblia'', is a flagellated parasitic microorganism of the genus ''Giardia'' that colonizes the small intestine, causing a diarrheal condition known as giardiasis. The ...
''. Centrins have therefore been present in the common ancestor of eukaryotes. Conversely, they have no recognizable
homolog In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of prima ...
s in
archea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeb ...
and
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
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 Pericentriolar material (PCM, sometimes also called pericent matrix) is a highly structured, dense mass of protein which makes up the part of the animal centrosome that surrounds the two centrioles. The PCM contains proteins responsible for microtub ...
. It is evident that some parts of the centrosome are highly diverged in the model species ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...
'' and ''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
''. 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 The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
. Thus, these flies have evolved functionally redundant machinery, which is independent of the centrosomes.


Associated nucleotides

Research in 2006 indicated that centrosomes from Atlantic 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 In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
databases. One identified RNA sequence contains a putative
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
, 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.


References

{{Organelles