Cell division is a controlled process necessary for life, growth, and tissue repair. At the heart of this process in animal cells is a significant organelle known as the centrosome. Often called the primary microtubule-organizing center (MTOC), the centrosome directs the process of mitosis, where one cell divides into two identical daughter cells. This function ensures that genetic information is passed on accurately from one generation of cells to the next.
The Centrosome Structure and Duplication Cycle
The centrosome has a distinct structure, consisting of two barrel-shaped centrioles positioned at right angles to each other. These centrioles are embedded in a dense, protein-rich cloud known as the pericentriolar material (PCM). While the centrioles provide a scaffold, the PCM initiates the growth of microtubules, the hollow protein filaments that form the cell’s internal skeleton. The PCM contains proteins, such as γ-tubulin, which are responsible for nucleating these microtubules.
For a cell to divide, it must first replicate its single centrosome. This duplication is timed to occur during the S phase of the cell cycle, running in parallel with the replication of the cell’s DNA. The process begins at the G1/S transition, where a new “procentriole” starts to form at the base of each parent centriole. These procentrioles gradually elongate throughout the S and G2 phases.
As the new centrioles mature, each pair begins to accumulate its own surrounding PCM, forming two complete centrosomes. By the time the cell is ready to enter mitosis, it possesses two distinct centrosomes, each containing a pair of centrioles. This duplication ensures that when the cell divides, each resulting daughter cell will inherit one complete centrosome.
Formation of the Mitotic Spindle
As the cell transitions from its growth phase into mitosis, the two newly formed centrosomes begin to migrate. They move apart to opposite ends of the nucleus to establish the two poles of the cell. This positioning creates a bipolar structure that will guide the separation of chromosomes. The centrosomes then assemble the mitotic spindle, an apparatus made of microtubules.
From each centrosome, microtubules rapidly polymerize, or grow outwards, in a star-like pattern referred to as an aster. These microtubules form the structural framework of the mitotic spindle. The spindle is composed of three distinct types of microtubules, each with a specific function. Astral microtubules radiate outward from the centrosome towards the cell’s outer membrane, anchoring the spindle and helping orient the plane of cell division.
Simultaneously, other microtubules extend from each centrosome toward the center of the cell. Some of these are polar microtubules, which overlap with their counterparts from the opposite pole. These overlapping microtubules interact to push the two poles apart, elongating the cell. The final type, kinetochore microtubules, also grow toward the cell’s center to find and attach to the chromosomes.
Orchestrating Chromosome Segregation
With the mitotic spindle established, the centrosomes direct chromosome alignment and separation. Kinetochore microtubules from each centrosome seek out and bind to specialized protein structures on the chromosomes called kinetochores. Each duplicated chromosome, made of two identical sister chromatids, has two kinetochores, one on each chromatid, allowing attachment to microtubules from opposite spindle poles.
This attachment creates a tension-based system that forces the chromosomes to align along the cell’s equator. This alignment, known as the metaphase plate, represents a checkpoint for the cell. The tension ensures that every chromosome is properly attached to the spindle before division proceeds. The cell will not progress until this alignment is complete.
Once all chromosomes are correctly positioned, the cell enters anaphase. During this stage, the connection holding the sister chromatids together is dissolved. The kinetochore microtubules then begin to shorten, pulling the separated chromatids toward the centrosome at their respective poles. This movement is driven by motor proteins that use energy to move along the microtubule fibers, delivering one complete set of chromosomes to each side of the dividing cell.
Consequences of Centrosome Abnormalities
The regulation of the centrosome number and function is important for accurate cell division. When this process fails, the consequences for the cell are severe. A common defect is centrosome amplification, where a cell ends up with more than two centrosomes. This often leads to the formation of multipolar spindles during mitosis, with microtubules pulling chromosomes in three or more directions instead of the usual two.
This chaotic segregation results in aneuploidy, a condition where daughter cells inherit an incorrect number of chromosomes. Aneuploidy is a characteristic of many cancer cells and contributes to tumor development by disrupting the balance of genes that control cell growth and division. An incorrect chromosome count can lead to the loss of tumor-suppressing genes or the amplification of cancer-promoting genes.
Beyond cancer, errors in centrosome function can also lead to developmental disorders. Because the orientation of the mitotic spindle is important for tissue formation during embryonic development, defects can have cascading effects. The placement of cells relies on the centrosome’s ability to orient the division axis, and failures in this process can contribute to certain genetic conditions and birth defects.