The Centrioles (Nucleus position and spatial arrangement of the cell), formation and function of flagella and cilia (ciliogenesis) and cell division (mitosis and meiosis).
Defects in the structure or number of centrioles in each cell can have considerable consequences for the physiology of an organism, causing alterations in the response to stress during inflammation, male infertility, neurodegenerative diseases and tumor formation, among others.
A centriol is a cylindrical structure. A pair of centrioles, surrounded by a dense mass of dense material (called"pericentriolar material", or PCM), forms a compound structure called centrosome.
They were considered unimportant until a few years ago, when it was concluded that they were the main organelles in the conduction of cell division and duplication (mitosis) in eukaryotic cells (mainly in humans and other animals).
The cell
The last common ancestor of all life on Earth was a single cell and the last common ancestor of all eukaryotes was a cell ciliated with centrioles.
Each organism is constituted by a group of cells that interact. Organisms contain organs, organs are composed of tissues, tissues are made up of cells and cells are made up of molecules.
All cells use the same molecular building blocks, similar methods for storage, maintenance and expression of genetic information, and similar processes of energy metabolism, molecular transport, signaling, development and structure.
The microtubules
In the early days of electron microscopy, cell biologists observed long tubules in the cytoplasm they called microtubules.
Morphologically similar microtubules were observed to form mitotic spindle fibers, as components of axons in neurons, and as structural elements in cilia and flagella.
Careful examination of individual microtubules indicated that they all consisted of 13 longitudinal units (now called protofilaments) consisting of a main protein (made up of a closely related α-tubulin subunit and a β-tubulin subunit) and several proteins associated with Microtubules (MAPs).
In addition to their functions in the rest of the cells, microtubules are essential in the growth, morphology, migration, and polarity of the neuron, as well as for development, maintenance and survival and an efficient nervous system .
The importance of a delicate interaction between the components of the cytoskeleton (microtubules, actin filaments, intermediate filaments and septins) is reflected in several human neurodegenerative disorders related to the abnormal dynamics of microtubules, including Parkinson's disease and the Alzheimer disease .
Cilia and flagella
Cilia and flagella are organelles found on the surface of most eukaryotic cells. They are constituted mainly by microtubules and membrane.
Sperm motility is due to mobile cytoskeletal elements present in their tail, called Axonemas . The structure of the axonemes consists of 9 groups of 2 microtubules each, molecular motors (dyneins) and their regulatory structures.
Centrioles play a central role in ciliogenesis and cell cycle progression. The maturation of the centrioles produces a change of function, which leads from the division of the cell to the formation of cilium.
Defects in the structure or function of the axonema or cilia cause multiple disorders in humans called ciliopathies. These diseases affect various tissues, including the eyes, kidneys, brain, lungs and sperm motility (which often leads to male infertility).
The centriol
Nine triplets of microtubules arranged around a circumference (forming a short hollow cylinder) are the"building blocks"and the main structure of a centriol.
For many years the structure and function of the centrioles were ignored, even though by the 1880s centrosomes had been visualized by light microscopy.
Theodor Boveri Published a seminal paper in 1888, describing the origin of the centrosome coming from the sperm after fertilization. In his short communication of 1887, Boveri wrote that:
"The centrosome represents the dynamic center of the cell; Its division creates the centers of daughter cells formed, around which all other cellular components are organized symmetrically... The centrosome is the true dividing organ of the cell, it mediates the cellular and nuclear division"(Scheer, 2014: 1) . [Author's translation].
Shortly after the mid-twentieth century, with the development of electron microscopy, the behavior of centrioles was studied and explained by Paul Schafer.
Unfortunately, this work was largely ignored because the interest of the researchers began to focus on Watson and Krick's findings on DNA.
The centrosome
A pair of centrioles, located adjacent to the nucleus and perpendicular to each other, are"centrosome". One of the centriolos is known as the"father"(or mother). The other is known as the"son"(or daughter, it is slightly shorter, and has its base attached to the base of the mother).
The proximal ends (at the junction of the two centrioles) are submerged in a"cloud"of proteins (perhaps up to 300 or more) known as the microtubule organization center (MTOC), as it provides the protein needed for construction Of the microtubules.
MTOC is also known as"pericentriolar material", and has negative charge. Conversely, the distal ends (remote from the connection of the two centrioles) are positively charged.
The pair of centrioles, together with the surrounding MTOC, are known as the centrosome.
Duplication of the centrosome
When the centrioles begin to double, the father and son separate slightly and then each centriol begins to form a new centriol at its base: the father with a new child, and the child with a new child of his own (a"grandson"), .
While doubling the centriol, nucleus DNA is also doubling and separating. That is, current research shows that duplication of the centriol and separation of DNA are, in some way, linked.
Cell duplication and division (mitosis)
The mitotic process is often described in terms of an initiating phase, known as the"interface,"followed by four phases of development.
During the interphase, the centrioles are duplicated and separated into two pairs (one of these pairs begins to move towards the opposite side of the nucleus) and the DNA divides.
After doubling the centrioles, the centrioles microtubules extend and line up along the major axis of the nucleus, forming the"mitotic spindle".
In the first of four stages of development (Phase I or"Profase"), the chromosomes condense and approach, and the nuclear membrane begins to weaken and dissolve. At the same time the mitotic spindle is formed with the pairs of centrioles now located at the ends of the spindle.
In the second phase (Phase II or"Metaphase"), the chains of the chromosomes align with the axis of the mitotic spindle.
In the third phase (Phase III or"Anaphase"), the chromosomal chains divide and move toward the opposite ends of the now enlarged mitotic spindle.
Finally, in the fourth phase (Phase IV or"Telophase"), new nuclear membranes are formed around the separated chromosomes, the mitotic spindle is undone and the cellular separation begins to be completed with half of the cytoplasm that goes with each new nucleus.
At each end of the mitotic spindle, the pairs of centrioles exert an important influence (apparently related to the forces exerted by the electromagnetic fields generated by the negative and positive charges of their proximal and distal ends) throughout the process of cell division.
The centrosome and immune response
The Stress exposure Influences the function, quality and duration of an organism's life. Stress generated, for example by an infection, can lead to inflammation of infected tissues, activating in the body the immune response. This response protects the affected organism, eliminating the pathogen.
Many aspects of the functionality of the immune system are well known. However, the molecular, structural, and physiological events in which the centrosome is implicated remain an enigma.
Recent studies have discovered unexpected dynamic changes in the structure, location and function of the centrosome under different conditions related to stress. For example, after mimicking the conditions of infection, an increase in PCM and microtubule production has been found in interphase cells.
The centrosomes in the immunological synapse
The centrosome plays a very important role in the structure and function of Immunological synapse (YES). This structure is formed by specialized interactions between a T cell and an antigen presenting cell (CPA). This cell-cell interaction initiates the migration of the centrosome into the SI and its subsequent coupling to the plasma membrane.
Coupling of the centrosome in the SI is similar to that observed during ciliogenesis. However, in this case, it does not initiate the assembly of the cilia, but participates in the organization of the IS and the secretion of cytotoxic vesicles to lyse the target cells, constituting a key organ in the activation of T cells.
Centrosome and heat stress
The centrosome is targeted by"molecular chaperones"(a set of proteins whose function is to assist in folding assembly and cellular transport of other proteins) that provide protection against exposure to heat shock and stress.
Stress factors affecting the centrosome include damage to DNA and heat (such as that of the cells of febrile patients). DNA damage initiates DNA repair pathways, which can affect centrosome function and protein composition.
Heat stress causes modification of the centriol structure, disruption of the centrosome and complete inactivation of its ability to form microtubules, altering the formation of the mitotic spindle and preventing mitosis.
Disruption of the centrosomes' function during fever could be an adaptive reaction to inactivate the spindle poles and prevent abnormal DNA division during mitosis, especially given the potential dysfunction of multiple proteins following heat induced denaturation.
Also, it could provide the cell extra time to recover its pool of functional proteins before restarting cell division.
Another consequence of the inactivation of the centrosome during fever is its inability to move to the SI to organize it and participate in the secretion of cytotoxic vesicles.
Abnormal development of centrioles
The development of centriol is a rather complex process, and although a number of regulatory proteins participate in it, different types of failure may occur.
If there is an imbalance in the proportion of proteins, the child centriol may be defective, its geometry may be distorted, the axes of one pair may deviate from perpendicularity, multiple centrioles may develop, the centrile may reach full length before Time, or decoupling of pairs may be delayed.
When there is wrong or erroneous duplication of centrioles (with geometric defects and / or multiple duplication), DNA replication is altered, chromosomal instability (CIN) occurs.
Likewise, centrosome defects (for example, an enlarged or enlarged centrosome) lead to CIN, and promote the development of multiple centrioles.
These developmental mistakes generate damages in the cells that can even lead to malignant.
Abnormal Centrioles and Malignant Cells
Thanks to the intervention of regulatory proteins, when anomalies are detected in the development of centrioles and / or centrosome, the cells can implement self-correction of the anomalies.
However, if self-correction of the anomaly is not achieved, abnormal centrioles or multiple children ("supernumerary centrioles") can lead to the generation of tumors ("tumorigenesis") or cell death.
Supernumerary centrioles tend to come together, leading to clustering of the centrosome ("centrosome amplification", characteristic of cancer cells), altering cell polarity and normal development of mitosis, resulting in the onset of tumors.
Cells with supernumerary centrioles are characterized by an excess of pericentriolar material, interruption of cylindrical structure or excessive length of centrioles and centrioles that are not perpendicular or misplaced.
It has been suggested that clusters of centrioles or centrosomes in cancer cells could serve as a"biomarker"in the use of therapeutic and imaging agents, such as super-paramagnetic nanoparticles.
References
- Borisy, G., Heald, R., Howard, J., Janke, C., Musacchio, A., & Nogales, E. (2016). Microtubules: 50 years on from the discovery of tubulin. Nature Reviews Molecular Cell Biology, 17 (5), 322-328.
- Buchwalter, R.A., Chen, J.V., Zheng, Y., & Megraw, T. L. Centrosome in Cell Division, Development and Disease. ELS.
- Gambarotto, D., & Basto, R. (2016). Consequences of Numerical Centrosome Defects in Development and Disease. In The Microtubule Cytoskeleton (pp. 117-149). Springer Vienna.
- Huston, R.L. (2016). A Review of Centriole Activity, and Wrongful Activity, during Cell Division. Advances in Bioscience and Biotechnology, 7 (03), 169.
- Inaba, K., & Mizuno, K. (2016). Sperm dysfunction and ciliopathy. Reproductive Medicine and Biology, 15 (2), 77-94.
- Keeling, J., Tsiokas, L., & Maskey, D. (2016). Cellular mechanisms of ciliary length control. Cells, 5 (1), 6.
- Lodish, H., Berk, A., Kaiser, C.A., Krieger, M., Bretscher, A., Ploegh, H., Amon, A., Martin, K.C. (2016). Molecular Cell Biology. New York: W. H. Freeman and Company.
- Matamoros, A.J., & Baas, P. W. (2016). Microtubules in health and degenerative disease of the nervous system. Brain Research Bulletin, 126, 217-225.
- Pellegrini, L., Wetzel, A., Grannó, S., Heaton, G., & Harvey, K. (2016). Back to the tubule: microtubule dynamics in Parkinson's disease. Cellular and Molecular Life Sciences, 1-26.
- Scheer, U. (2014). Historical roots of centrosome research: discovery of Boveri's microscope slides in Würzburg. Phil. Trans. R. Soc. B, 369 (1650), 20130469.
- Severson, A.F., von Dassow, G., & Bowerman, B. (2016). Chapter Five-Oocyte Medium Spindle Assembly and Function. Current topics in developmental biology, 116, 65-98.
- Soley, J.T. (2016). A comparative overview of the sperm centriolar complex in mammals and birds: Variations on a theme. Animal reproduction science, 169, 14-23.
- Vertii, A., & Doxsey, S. (2016). The Centrosome: The Phoenix Organelle of the Immune Response. Single Cell Biology, 2016.
- Vertii, A., Hehnly, H., & Doxsey, S. (2016). The Centrosome, the Multitalented Renaissance Organelle. Cold Spring Harbor Perspectives in Biology, 8 (12), a025049.
- Activation T lymphocytes. Original work of the US Federal Government - public domain. Translated by BQmub2012110.
- Alejandro Porto - Derived from File: Aufbau einer Tierischen Zelle.jpg by Petr94. Basic scheme of an animal eukaryotic cell.
- Kelvinsong - Centrosome Cycle (editors version).svg. Translated into Spanish by Alejandro Porto.
- Kelvinsong - Own work. Diagram of a centrosome, without the yellow frame.
- Kelvinsong, Centriole-en, CC BY 3.0.
- NIAID / NIH - NIAID Flickr's photostream. Micrograph of a human T lymphocyte (also called T cell) of the immune system of a healthy donor.
- Silvia Márquez and Andrea Lassalle, Tubulina, CC BY 3.0
- Simplified spermatozoon diagram.svg: Mariana Ruiz derivative work: Miguelferig.