The centrosome is an intracellular organelle whose primary function is to organize the microtubules of the cell. Microtubules can be thought of as the cell’s skeleton, so centrosomes are the organelles that serve as the lynchpin and scaffolding that organizes and anchors the cellular skeleton.
Centrosomes also play a role in cellular mitosis—the process by which a cell reproduces by splitting into two identical copies. Centrosomes help form the mitotic spindle which is the structure that attaches to the chromosomes and pulls them apart during mitosis. The centrosome was first discovered in 1883 by Eduoard Van Beneden and given its official name in 1888.
Centrosomes are only found in eukaryotic metazoans (multicellular animals). In eukaryotic organisms, centrosomes serve as the microtubule organizing center (MTOC) of the cell. Plants and fungi use other MTOC structure to organize their microtubules. In multicellular animals, centrosomes are one of the main reasons cells have a well-defined shape and structure.
The centrosome organizes the microtubules in an efficient radial pattern, which keeps the cell in its shape. The centrosome also provides a center from which to begin cell division, which prevents errors in copying during cellular mitosis. Cells that do not have centrosomes tend to be less efficient at mitosis, as the lack of a central organizing structure prevents the cell from finding a suitable localization site to begin mitosis.
Composition/Structure of Centrosomes
Centrosomes are an organelle complex composed of two subunits called centrioles arranged perpendicularly to each other. Surrounding the complex is a mesh of various proteins called the pericentriolar material. The pericentriolar material contains the proteins responsible for microtubule assembly and anchoring; γ-tubulin, pericentrin, and ninein. The pericentriolar material holds the centrioles together and serves as binding sites for the microtubules.
Each centriole itself is composed of a series of microtubules arranged in a tube-like shape. Microtubules are composed of two kinds of proteins: α-tubulin and β-tubulin. Microtubules form when dimers of α-tubulin and β-tubulin concatenate into polarized chains. These polarized chains then arrange in a circular pattern around a single radial axis. Most commonly, each centriole is composed out of 27 individual chains of microtubules, arranged radially in groups of 3. In a handful of organisms, centrioles either have a different number of microtubules, or they lack radial symmetry. Fruit flies, for example, have centriole composed out of double strands of microtubules, instead of triple strands.
Each centrosome contains two centrioles, termed the mother and daughter centriole. The mother centriole is the older one of the pair. During the DNA replication which precedes cellular division, 2 new centrioles will form at the proximal ends of the existing mother and daughter centrioles. These newly constructed centrioles each become a daughter in the new pair. During mitosis, the original mother-daughter pair will separate as the cell splits, giving a mother-daughter pair to each new cell formed during mitosis. Both the mother and daughter centriole are tied together with fibers located at the proximal end of each centriole.
Compared to other microtubules structures, centrosomes are very robust and stable. Most microtubules degrade rather quickly, which is why the cell is constantly working to produce them. Centriole microtubules, on the other hand, are held together with special centriole -specific proteins that contribute to long-term stability. It is also thought that this increased stability is in part due to post-construction modifications of centriole microtubules. There also appears to be some mechanism which regulates centriole length, though there is still not an in-depth understanding of length-regulating mechanisms.
Functions Of Centrosomes
The main function of the centrosomes is to stimulate the production of and organize the distribution and orientation of microtubules in the cell. Microtubules play many functions in the cell, from giving it shape/structure to acting as a sort of “highway” for intracellular transport. As such, the action of the centrioles in creating and organizing microtubules affects virtually every other operation of the cell by providing the physical framework upon which the cell operates.
Centrosomes are able to spatially orient microtubules in virtue of microtubules’ intrinsic polarity. Each microtubule has a + end and a – end, which determines how it interacts with other cellular structures. The – end of the microtubules are drawn to the centrosome, so they will attach with the + end facing towards the exterior of the cell. Since centrioles, and centrosomes by extension, are responsible for microtubule nucleation, they can determine the location and orientation of microtubules. Proteins in the pericentriolar material stimulate the production of tubulin proteins. γ-tubulin located in the pericentriolar material is arranged in a ring-like complex that mimics the + polarized end, giving the – end of microtubules a site to bond to.
Centrosomes play a major role in cellular reproduction. Centrosomes form the core of the mitotic spindle, the appendage that separates sister chromatids during mitosis. During DNA replication, the first step of cellular division, the centrosome complex is copied. After forming, the two centrosomes (each containing two centrioles) migrate to opposite ends of the cell and begin to construct the mitotic spindle. At this point, the membrane surrounding the nucleus of the cell dissolve, exposing the chromosomes.
The spindle is composed mostly out of microtubules which connect with the cell’s chromosomes through the action of special proteins called kinetochores. The location of the two centrosomes on either pole of the cells align the two chromosomes on top of each other. This realignment of the cell’s chromosomes is necessary for accurate chromosomal division and to specify the plane of cell division. The central line through the cell that represents the plane of division is called the metaphase plate.
One the spindle apparatus has its + ends attached to the chromosomes and its – ends attached to the centrosome located at the cell’s poles, the actual division of the cell occurs. In the central section of the spindle apparatus, microtubules will depolymerize, causing them to contract and to exert tension in the direction of either pole. The attached chromosomes are then pulled apart and reorganized into two distinct nuclei each with a pair of chromosomes. Lastly, the cellular cytoplasm divides and produces two identical cells.
Although highly involved in the process of mitosis, it seems that centrosomes are not necessary for cell division. As stated previously, plant and fungal cells lack centrosomes, yet still undergo mitosis. In plant and fungal cells, some other cellular structure takes on the role as the microtubule organization center. Even in eukaryotes, centrosomes do not seem to be necessary for mitosis.
Experiments with the common fruit fly Drosophila show that cell division can occur even when the centrosomes have been disabled. Thus, it is thought that centrosome’s primary purpose is not to make cellular division possible, but to make it much more efficient and accurate. Cells that lack centrosomes are more likely to replicate incorrectly, leading to premature cell death, incorrect physical development or potentially deleterious genetic mutations. Fruit flies, for instance, can develop from larvae into adults without any centrosomes. During development, the cells arrange themselves normally without the action of the centrosomes. However, fruit flies that develop in such a way will die shortly after reaching adulthood, as their sensory cells do not develop the proper cilia.
Centrosome Aberration And Cancer
Aberrations and defects in centrosome structure and functioning have been associated with a variety of cancers and tumorous growths. Cancerous cells tend to have centrosomes that are too big due to an excess of pericentriolar material. Additionally, tumors often contain cells with an inappropriate amount of centrosomes. The genesis of an incorrect number of centrosomes has a number of potential mechanisms, most related to genomic instability due to improper DNA replication.
In 1902, German biologist Theodor Boveri hypothesized that increased numbers of centrosomes in cells cause cancer. He reasoned that the overzealous activity of the centrosomes in dividing cells compromises the integrity of the chromosomes, resulting in genomic instability and the formation of malignant tumors. Although his original theory was accurate in many respects, at this point, the exact causal relationship between centrosome amplification and cancer is not known. It is likely that centrosome aberration provides a kind of feedback mechanism for the progression of cancerous tumors. The presence of aberrated centrosomes contributes to improper cellular division, which leads to more tumorous cells with aberrated centrosomes and so on.
Evolution Of Centrosomes
Centrosomes are an evolutionarily old organelle as they are present in a number of early eukaryotic species. The genes that code for centrosomes are called centrins and are present in the earliest common ancestors of all eukaryotic organisms. In contrast, archaea and bacteria do not have any genes analogous to centrins, so the presence of centrins constitutes a unique feature of eukaryotic organisms. Species such as the fruit fly have lost one of the two main groups of centrins, which explains their anomalous centrosome structure.