The Centriole’s Role Throughout the Cell Cycle
Explore how the centriole transitions through the cell cycle, from ensuring accurate chromosome segregation to building essential sensory and signaling structures.
Within the cytoplasm of animal cells and some lower plants lie centrioles, microscopic, barrel-shaped organelles composed of proteins. Centrioles are a component of the centrosome, the cell’s primary microtubule-organizing center. The centrosome organizes the microtubules that form the cell’s internal skeletal system, which helps establish the positions of the nucleus and other organelles.
The centriole’s most recognized function is in cell division, where it facilitates the formation of the mitotic spindle responsible for segregating chromosomes into two daughter cells. The centriole’s role also extends beyond mitosis to include the formation of cilia and flagella, which are involved in cell motility and signaling.
Centriole Duplication and Maturation
The precise replication of centrioles ensures that each daughter cell inherits a single centrosome. This duplication process is controlled to occur only once per cycle, beginning in the S phase and concluding in the G2 phase. Regulation starts in the G1 phase with a “licensing” step that prepares existing centrioles for duplication but prevents premature replication.
Duplication follows a semi-conservative mechanism, where each of the two “mother” centrioles serves as a template for a new “daughter” centriole. The new daughter centriole assembles at a right angle to the mother, creating a distinct orthogonal arrangement. This formation begins with the assembly of a short procentriole attached to the side of the mother centriole.
Following their initial formation, these new centrioles undergo maturation. This involves the recruitment of a dense mass of proteins known as the pericentriolar material (PCM). The expansion of the PCM endows the new centrosome with the capacity to organize microtubules effectively, acquiring the full competence needed for the upcoming mitosis.
Centrioles in Mitotic Spindle Formation
As a cell transitions from interphase into mitosis, the two duplicated centrosomes migrate to opposite sides of the nucleus during prophase. This establishes the two poles of the forthcoming mitotic spindle. Each centrosome acts as a focal point from which microtubules, the protein filaments that make up the spindle, grow and radiate outwards.
The microtubules extend from each pole, with some connecting to protein structures on the chromosomes called kinetochores, while others overlap in the middle of the cell. Once the mitotic spindle is fully formed, it captures the condensed chromosomes.
During metaphase, the spindle fibers adjust their lengths, pushing and pulling the chromosomes until they are aligned at the cell’s equator, a region known as the metaphase plate. In the subsequent anaphase stage, the connections between sister chromatids are severed. The spindle fibers then shorten, pulling the separated chromatids towards opposite poles of the cell, ensuring each new daughter cell receives a complete set of chromosomes.
Post-Mitotic Centriole Functions and Ciliogenesis
After mitosis, the centrioles within the new daughter cells undergo disengagement. The orthogonal connection between the mother and daughter centriole in each pair is broken. This separation, occurring late in mitosis or early in the G1 phase, is a resetting mechanism that licenses the centrioles for the next round of duplication.
During interphase, particularly in cells that enter a quiescent state (G0) or are in the G1 phase, the older mother centriole can take on a new function. It can migrate and anchor to the inner surface of the plasma membrane, where it becomes a basal body. This docked basal body then serves as a template for the assembly and growth of a primary cilium.
Primary cilia are solitary, antenna-like structures that extend from the surface of most vertebrate cells. These cilia are non-motile and function as sensory organelles that detect signals from the extracellular environment. The formation of a primary cilium is often associated with cell cycle exit, indicating a switch from proliferation to differentiation or sensory functions.
Centriole Aberrations and Cellular Impact
Deviations from the regulated centriole cycle can lead to cellular dysfunction. Errors in duplication can result in an abnormal number of centrioles, a condition known as centriole amplification. Cells with more than the normal two centrosomes, or supernumerary centrioles, face challenges during cell division. These extra centrosomes can lead to the formation of multipolar mitotic spindles, where chromosomes are pulled in more than two directions.
The consequence of such multipolar divisions is often chromosome mis-segregation. Daughter cells may inherit an incorrect number of chromosomes, a state called aneuploidy. This genomic instability is a common characteristic of many human cancers and is thought to contribute to tumor progression.
Conversely, the loss of centrioles can impair cell processes, though some cell types can divide without them. More commonly, defects in the structure or function of centrioles as basal bodies disrupt the formation of cilia. This leads to a class of human genetic disorders known as ciliopathies. Because cilia are present on many cell types, these disorders can affect multiple organs and lead to a wide range of diseases.