Microtubule dynamics, like those of actin filaments, are profoundly influenced by the binding and hydrolysis of nucleotide—GTP in this case. GTP hydrolysis occurs only within the β-tubulin subunit of the tubulin dimer. It proceeds very slowly in free tubulin subunits but is accelerated when they are incorporated into microtubules. Following GTP hydrolysis, the free phosphate group is released and the GDP remains bound to β-tubulin within the microtubule lattice. Thus, as in the case of actin filaments, two different types of microtubule structures can exist, one with the “T form” of the nucleotide bound (GTP) and one with the “D form” bound (GDP). The energy of nucleotide hydrolysis is stored as elastic strain in the polymer lattice, making the free-energy change for dissociation of a subunit from the D-form polymer more negative than the free-energy change for dissociation of a subunit from the T-form polymer. In consequence, the ratio of koff/kon for GDP-tubulin (its critical concentration [Cc(D)]) is much higher than that of GTP-tubulin. Thus, under physiological conditions, GTP-tubulin tends to polymerize and GDP-tubulin to depolymerize.
Whether the tubulin subunits at the very end of a microtubule are in the T or the D form depends on the relative rates of GTP hydrolysis and tubulin addition. If the rate of subunit addition is high—and thus the filament is growing rapidly— then it is likely that a new subunit will be added to the polymer before the nucleotide in the previously added subunit has been hydrolyzed. In this case, the tip of the polymer remains in the T form, forming a GTP cap. However, if the rate of subunit addition is low, hydrolysis may occur before the next subunit is added, and the tip of the filament will then be in the D form. If GTP-tubulin subunits assemble at the end of the microtubule at a rate similar to the rate of GTP hydrolysis, then hydrolysis will sometimes “catch up” with the rate of subunit addition and transform the end to a D form. This transformation is sudden and random, with a certain probability per unit time that depends on the concentration of free GTP-tubulin subunits.
Suppose that the concentration of free tubulin is intermediate between the critical concentration for a T-form end and the critical concentration for a D-form end (that is, above the concentration necessary for T-form assembly, but below that for the D form). Now, any end that happens to be in the T form will grow, whereas any end that happens to be in the D form will shrink. On a single microtubule, an end might grow for a certain length of time in a T form, but then suddenly change to the D form and begin to shrink rapidly, even while the free subunit concentration is held constant. At some later time, it might then regain a T-form end and begin to grow again. This rapid interconversion between a growing and shrinking state, at a uniform free subunit concentration, is called dynamic instability (Figure 16–44A and Figure 16–45; see Panel 16–2). The change from growth to shrinkage is called a catastrophe, while the change to growth is called a rescue.