Mitosis is a fundamental cellular process that allows a single cell to divide into two genetically identical daughter cells. This precise division is essential for growth, tissue repair, and reproduction in many organisms. Microtubules, dynamic components within cells, are central to orchestrating the intricate stages of this division. Their structural and dynamic properties enable the cell to accurately partition its genetic material.
Microtubules: The Cell’s Dynamic Scaffolding
Microtubules are hollow, cylindrical protein filaments that are part of the cell’s cytoskeleton. They are constructed from repeating units of a globular protein called tubulin, which exists as a dimer of alpha and beta tubulin. These tubulin dimers polymerize to form 13 linear protofilaments that assemble around a hollow core, giving the microtubule its characteristic structure. Microtubules are dynamic structures, constantly undergoing cycles of growth (polymerization) and shrinkage (depolymerization), a process termed dynamic instability. This dynamic behavior is regulated by the hydrolysis of guanosine triphosphate (GTP) bound to beta-tubulin, which influences the stability of the microtubule ends.
Building the Mitotic Spindle
As a cell prepares for division, its microtubule network undergoes a significant reorganization to form the mitotic spindle. In animal cells, specialized structures called centrosomes function as microtubule-organizing centers (MTOCs). During interphase, the centrosome duplicates, and just before mitosis, these two centrosomes move to opposite sides of the nucleus, establishing the poles of the developing spindle. From these poles, microtubules nucleate and grow, radiating outwards.
The mitotic spindle is composed of three main types of microtubules, each with a distinct role in spindle organization. Kinetochore microtubules extend from the spindle poles and directly attach to protein structures called kinetochores, which are located on the centromere region of each chromosome. Polar, or interpolar, microtubules also originate from the spindle poles but extend towards the cell’s equator, where they overlap with microtubules from the opposite pole. Astral microtubules radiate outwards from the spindle poles towards the cell periphery, helping to anchor the spindle within the cell and influence spindle positioning.
Orchestrating Chromosome Movement
Microtubules play a central role in the precise alignment and separation of chromosomes during metaphase and anaphase. During metaphase, kinetochore microtubules from opposite spindle poles attach to the kinetochores of sister chromatids. Through cycles of polymerization and depolymerization, and in conjunction with motor proteins, these microtubules exert pulling and pushing forces on the chromosomes. This dynamic interplay positions all chromosomes at the cell’s equator, forming the metaphase plate. Proper alignment involves a tension-sensing mechanism at the kinetochore, ensuring each sister chromatid attaches correctly to microtubules from opposing poles.
Once alignment is complete, the cell proceeds to anaphase, where sister chromatids are separated and moved to opposite poles of the cell. This segregation occurs through two main mechanisms: anaphase A and anaphase B.
In anaphase A, kinetochore microtubules shorten, primarily by depolymerization at their plus ends near the kinetochores, pulling the sister chromatids towards the spindle poles. Concurrently, motor proteins like dynein and kinesin, which move along the microtubules, contribute to this poleward movement.
In anaphase B, the spindle poles themselves move further apart, leading to the elongation of the cell. This separation is largely driven by the lengthening of polar microtubules, which slide past each other at the spindle midzone, again facilitated by motor proteins. Both anaphase A and B occur to ensure efficient and accurate distribution of genetic material.
Completing Cell Division
Microtubules also contribute to the final stages of cell division, telophase and cytokinesis. During telophase, the separated chromosomes arrive at the spindle poles, and new nuclear envelopes begin to form around each set of chromosomes. Simultaneously, the mitotic spindle disassembles, and the cell prepares for physical division.
In cytokinesis, the process by which the cytoplasm divides, microtubules play a role in defining the plane of cell division and in the final separation of the daughter cells. While the contractile ring, primarily composed of actin filaments, generates the force to pinch the cell in two, remnants of the polar microtubules form a transient structure known as the midbody. The midbody is a dense bundle of microtubules and associated proteins that persists in the narrow intercellular bridge connecting the two nascent daughter cells. This structure is important for the final abscission, ensuring the physical separation of the two daughter cells.