Centriolos: Functions And Characteristics

The centrioles  are cylindrical structures composed of cell clusters of microtubules. They are made up of the protein tubulin, which is found in most eukaryotic cells.

An associated pair of centrioles, surrounded by a shapeless mass of dense material called pericentriolar material (PCM), make up a structure called the centrosome.

The function of the centrioles is to direct the assembly of microtubules, participating in cell organization (position of the nucleus and spatial arrangement of the cell), formation and function of flagella and cilia (ciliogenesis) and cell division (mitosis and meiosis).

Centrioles are found in cellular structures known as centrosomes in animal cells and are absent in plant cells.

Defects in the structure or number of centrioles in each cell can have considerable consequences for the physiology of an organism, producing alterations in the response to stress during inflammation, male infertility, neurodegenerative diseases and tumor formation, among others.

A centriole is a cylindrical structure. A pair of associated centrioles, surrounded by a shapeless mass of dense material (called “pericentriolar material,” or PCM), form a composite structure called a “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 ciliated cell with centrioles.

Each organism is made up of a group of interacting cells. Organisms contain organs, organs are made up 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 the storage, maintenance, and expression of genetic information, and similar processes of energy metabolism, molecular transport, signaling, development, and structure. 

Microtubules

In the early days of electron microscopy, cell biologists observed long tubules in the cytoplasm that they called microtubules.

Morphologically similar microtubules were observed forming the fibers of the mitotic spindle, as components of the axons of neurons, and as structural elements in cilia and flagella.

Careful examination of the individual microtubules indicated that they were all made up of 13 longitudinal units (now called protofilaments) made up of a major protein (made up of a closely related α-tubulin and a closely related β-tubulin subunit) and several proteins associated with microtubules (MAPs).

In addition to their functions in other cells, microtubules are essential in the growth, morphology, migration, and polarity of the neuron, as well as for the development, maintenance and survival and of an efficient nervous system .

The importance of a delicate interaction between components of the cytoskeleton (microtubules, actin filaments, intermediate filaments, and septins) is reflected in several human neurodegenerative disorders related to abnormal microtubule dynamics, including Parkinson’s disease and Alzheimer’s 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 its tail, called axonemes. The structure of 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. Centriole maturation produces a change in function, leading from cell division to cilium formation.

Defects in the structure or function of the axoneme 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 centriole

Centrioles are cylindrical structures that are made up of clusters of microtubules. Most centrioles are made up of nine sets of microtubule trios, arranged in a cylinder.

Nine triplets of microtubules arranged around a circumference (forming a short hollow cylinder), are the “building blocks” and the main structure of a centriole. 

For many years the structure and function of the centrioles was ignored, despite the fact that by the 1880s the centrosome had been visualized by light microscopy.

Theodor Boveri published a seminal work in 1888, describing the origin of the centrosome from 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 the daughter cells formed, around which all the other cellular components are organized symmetrically… The centrosome is the true dividing organ of the cell, it mediates nuclear and cellular division ”(Scheer, 2014: 1) . [Author’s translation].

Shortly after the mid-20th century, with the development of electron microscopy, the behavior of centrioles was studied and explained by Paul Schafer.

Unfortunately, this work was ignored in large part because researchers were beginning to focus on the findings of Watson and Krick on DNA. 

The centrosome

A pair of centrioles, located adjacent to the nucleus and perpendicular to each other, are “a centrosome.” One of the centrioles 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 connection of the two centrioles) are immersed in a protein “cloud” (perhaps up to 300 or more) known as the microtubule organizing center (MTOC), as it provides the protein necessary for construction microtubules.

MTOC is also known as “pericentriolar material,” and it is negatively charged. Conversely, the distal ends (away from the connection of the two centrioles) are positively charged.

The pair of centrioles, along with the surrounding MTOC, are known as the “centrosome.” 

Centrosome duplication

When the centrioles begin to duplicate, the father and son separate slightly and then each centriole begins to form a new centriole at its base: the father with a new son, and the son with a new son of his own (a “grandson”). .

While centriole duplication occurs, the nucleus DNA is also duplicating and separating. That is, current research shows that centriole duplication and DNA separation are somehow linked. 

Cell duplication and division (mitosis)

The mitotic process is often described in terms of an initiator phase, known as “interface,” followed by four developmental phases.

During the interphase, the centrioles duplicate and separate into two pairs (one of these pairs begins to move towards the opposite side of the nucleus) and the DNA divides.

After the duplication of the centrioles, the microtubules of the centrioles extend and align themselves along the major axis of the nucleus, forming the “mitotic spindle”.

In the first of the four phases of development (Phase I or “Prophase”), the chromosomes condense and move closer together, 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 are aligned with the axis of the mitotic spindle.

In the third phase (Phase III or “Anaphase”), the chromosomal chains divide and move to opposite ends of the now elongated mitotic spindle.

Finally, in the fourth phase (Phase IV or “Telophase”), new nuclear membranes are formed around the separated chromosomes, the mitotic spindle falls apart and the cell separation begins to be completed with half of the cytoplasm that goes with each new nucleus.

At each end of the mitotic spindle, the centriole pairs exert an important influence (apparently related to the forces exerted by the electromagnetic fields generated by the negative and positive charges at its proximal and distal ends) during the entire process of cell division. 

The Centrosome and the Immune Response

Exposure to stress influences the function, quality and length of life of an organism. The stress generated, for example by an infection, can lead to inflammation of the infected tissues, activating the immune response in the body. 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 involved remain an enigma.

Recent studies have discovered unexpected dynamic changes in the structure, location, and function of the centrosome under different stress-related conditions. For example, after mimicking the conditions of an infection, increased PCM and microtubule production has been found in interphase cells.

Centrosomes at the immune synapse

The centrosome plays a very important role in the structure and function of the immunological synapse (SI). This structure is formed by specialized interactions between a T cell and an antigen presenting cell (APC). This cell-cell interaction initiates the centrosome migration towards the SI and its subsequent coupling to the plasma membrane.

The centrosome coupling in the SI is similar to that observed during ciliogenesis. However, in this case, it does not initiate the assembly of the cilia, but rather participates in the organization of the SI and the secretion of cytotoxic vesicles to lyse the target cells, becoming a key organ in the activation of T cells.

The Centrosome and Heat Stress

The centrosome is the target of “molecular chaperones” (set of proteins whose function is to help the folding, assembly and cellular transport of other proteins) that provide protection against exposure to heat shock and stress.

Stressors that affect the centrosome include DNA damage and heat (such as that experienced by the cells of feverish patients). DNA damage initiates DNA repair pathways, which can affect centrosome function and protein composition.

The stress generated by heat causes modification of the centriole structure, the disruption of the centrosome and the complete inactivation of its ability to form microtubules, altering the formation of the mitotic spindle and preventing mitosis.

Disruption of the function of the centrosomes 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 after heat-induced denaturation.

Also, it could give 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 transfer to the SI to organize it and participate in the secretion of cytotoxic vesicles.

Abnormal development of the centrioles

The development of the centriole is a quite complex process and, although a series of regulatory proteins participate in it, different types of failures can occur.

If there is an imbalance in the ratio of the proteins, the daughter centriole may be defective, its geometry may be distorted, the axes of a pair may deviate from perpendicularity, multiple daughter centrioles may develop, the daughter centriole may reach full length before time, or the decoupling of the pairs may be delayed.

When there is a wrong or wrong duplication of centrioles (with geometric defects and / or multiple duplication), DNA replication is altered, chromosomal instability (CIN) occurs.

Similarly, centrosome defects (eg, an enlarged or enlarged centrosome) lead to CIN, and promote the development of multiple daughter centrioles.

These developmental errors generate damage to cells that can even lead to malignant disease.

Abnormal centrioles and malignant cells

Thanks to the intervention of regulatory proteins, when abnormalities are detected in the development of the centrioles and / or the centrosome, the cells can implement self-correction of the abnormalities.

However, if self-correction of the abnormality is not achieved, abnormal or multiple-daughter centrioles (“supernumerary centrioles”) can lead to the generation of tumors (“tumorigenesis”) or cell death.

The supernumerary centrioles tend to coalesce, leading to the grouping of the centrosome (“centrosome amplification”, characteristic of cancer cells), altering cell polarity and the normal development of mitosis, resulting in the appearance of tumors.

Cells with supernumerary centrioles are characterized by an excess of pericentriolar material, interruption of the cylindrical structure, or excessive length of the centrioles and centrioles that are not perpendicular or poorly placed.

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

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