Instabiliteit van microtubuli

In eukaryotic cells, during cell division, microtubules form the main components of the mitotic spindle and are required for chromosome segregation.

Microtubules are extremely dynamic. Individual microtubules grow, shrink, and rapidly alternate between the growing and shortening phases. Microtubules exhibit dynamic instability, the unpredictable change between growth and shrinkage.

The shift from growth to shrinkage is called a catastrophe and the shift from shrinkage to growth is called a rescue. At any point in time, a group of microtubules is actively assembling, while others are rapidly disassembling.

Microtubules nucleate and grow by the end-to-end polymerization of GTP-bound tubulin heterodimers. The tubulin heterodimer comprises an alpha and beta subunit.

The beta-tubulin subunit is bound to a hydrolyzable form of GTP. The hydrolysis of GTP to GDP destabilizes the microtubule framework. The structure splays out at the tip and the effect propagates down, causing depolymerization of the microtubule.

A variety of regulatory proteins control microtubule dynamics. Several microtubule-associated proteins or MAPs promote microtubule stability, while several other proteins, the catastrophe factors, destabilize the microtubules. Cells alter the activity of regulatory proteins to change microtubule dynamics dependent upon the phase of the cell cycle.

For example, during interphase, most animal cells contain a cytoplasmic array of long microtubules radiating from a single centrosome. As cells transition to the mitotic phase and duplicated centrosomes move towards the opposite poles, microtubule instability increases.

Microtubule instability facilitates the formation of a dense, dynamic array of mitotic microtubules, contributing to the spindle formation.