18.7 : Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and disassembly. This characteristic dynamic instability can be found both in vivo and in vitro.

Dynamic Instability

Individual microtubules may elongate and shrink simultaneously on the opposite ends at a given point in time. Whether a microtubule is growing or shrinking is determined by its rates of catastrophe and rescue. Catastrophe is when a growing microtubule begins to shorten rapidly. Rescue is the shift of a shrinking microtubule to elongate rapidly. The rate of β-tubulin bound-GTP hydrolysis is a primary factor that determines the dynamic instability.

In the cell, both free tubulin subunits and their αβ-heterodimeric forms are present in the cytoplasmic pool. The polymerization of tubulin subunits initiates when GTP-bound αβ-heterodimeric subunits are above a threshold concentration, referred to as the critical concentration for microtubule polymerization. β-tubulin exists in two forms. The GTP-bound-β-tubulin or T-form is responsible for the elongation and stable linear structure of microtubules. In contrast, the GDP-bound-β-tubulin or D-form favors microtubule disassembly. The GTP-bound-β-tubulins at the growing end act as a cap, preventing protofilament curvature and promoting elongation. Upon hydrolysis of GTP, the conformation of β-tubulin is slightly altered, resulting in protofilament curving. This curving facilitates the binding of destabilizing proteins like stathmin and kinesin-13 to remove the αβ-tubulin heterodimers.

Factors regulating the instability

Microtubule-associated proteins or the MAPs are critical regulators of microtubule dynamic instability. MAPs are broadly classified as stabilizers and destabilizers based on their function in microtubule dynamics. The stabilizer MAPs bind with the microtubules to reduce the catastrophe event and to promote elongation. On the other hand, the destabilizers bind to promote the catastrophe. Stabilizer MAPs are dominant during the interphase and in axonal and dendritic microtubules of neurons, promoting stable assemblies. During mitosis, destabilizer MAPs are more common. These MAPs are responsible for the chromosome segregation and the disassembly of the cytoskeletal mesh for cell division.