Question

What role do guanine nucleotides play in the catastrophic collapse and rescue of microtubules?

Answer 1

            Microtubules are protein polymers made of α/β tubulin heterodimers that form an essential part of the cytoskeleton of all eukaryotic cells. Besides giving structural stability and rigidity to a cell, microtubules play key roles in many physiological processes such as intracellular vesicle transport and chromosome separation during mitosis. An individual microtubule is a hollow cylinder of 25 nm diameter built usually from 13 protofilaments. While the stable subunits of microtubules are actually heterodimers composed of α and β monomers, we will refer to them for simplicity as monomers.

            These monomers exist in two different energetic states, namely bound to a molecule of guanosine triphosphate (GTP) or guanosine diphosphate (GDP), respectively. Only the GTP bound monomers are assembly competent meaning they are able to polymerize into microtubules. After the GTP monomers have been added to the growing microtubule, GTP bound to β tubulin is rapidly hydrolyzed (dephosphorylated) to form a bound GDP subunit. It has been hypothesized since the early 1980s that the so-called GTP cap on the tip of the growing microtubule gives rise to the stability of the microtubule. Once the GTP cap is lost, the microtubule will switch to a “collapsing” state, referred to as a catastrophe which is characterized by rapid depolymerization of the microtubule into its free subunits.

            However, there is also a possibility that at some point in time a catastrophically shrinking microtubule acquires a new GTP cap and thereby returns to the growing population, a situation that is referred to in the literature as a rescue event.