Dynamic instability 30 years later: complexities in microtubule growth and catastrophe

Abstract

Microtubules are not like other polymers. Whereas polymers such as F-actin will grow continuously as long as the subunit concentration is high enough, a steadily growing microtubule can suddenly shrink even when there is ample αβ-tubulin around. This remarkable behavior was discovered in 1984 when Tim Mitchison and Marc Kirschner deduced that microtubules switch from growth to shrinkage when they lose their GTP caps. Here, I review the canonical explanation of dynamic instability that was fleshed out in the years after its discovery. Many aspects of this explanation have been recently subverted, particularly those related to how GTP-tubulin forms polymers and why GTP hydrolysis disrupts them. I describe these developments and speculate on how our explanation of dynamic instability can be changed to accommodate them.

FIGURE 1:

Complexities in microtubule growth and catastrophe. (A) Schematic drawing of the 2D model for microtubule growth, showing a tapered microtubule end. The number of lateral bonds that form depends on the context at each protofilament end. (B) Schematic drawing of curvature at microtubule ends, showing a cross section of a growing microtubule end and its tapered, outwardly curved, and flattened-out structure. The schematic is based on cryo–electron microscopy images in Chrétien et al. (1995). (C) Schematic drawing of a patchwork GTP cap. The different colors of β-tubulin (red, green, blue, beige) represent hypothetical nucleotide states from GTP to GDP. (D) Schematic drawing of the aging process showing a young microtubule (far left, in diaper) growing and maturing (left to right, a teenager with headphones and an adult with necktie) until it becomes old (far right, with cane). The aging process leads to catastrophe.