The where, when and how of microtubule nucleation - one ring to rule them all

The function of microtubules depends on their arrangement into highly ordered arrays. Spatio-temporal control over the formation of new microtubules and regulation of their properties are central to the organization of these arrays. The nucleation of new microtubules requires gamma-tubulin, an essential protein that assembles into multi-subunit complexes and is found in all eukaryotic organisms. However, the way in which gamma-tubulin complexes are regulated and how this affects nucleation and, potentially, microtubule behavior, is poorly understood. gamma-tubulin has been found in complexes of various sizes but several lines of evidence suggest that only large, ring-shaped complexes function as efficient microtubule nucleators. Human gamma-tubulin ring complexes (gamma TuRCs) are composed of gamma-tubulin and the gamma-tubulin complex components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein family. Recent work has identified additional unrelated gamma TuRC subunits, as well as a large number of more transient gamma TuRC interactors. In this Commentary, we discuss the regulation of gamma TuRC-dependent microtubule nucleation as a key mechanism of microtubule organization. Specifically, we focus on the regulatory roles of the gamma TuRC subunits and interactors and present an overview of other mechanisms that regulate gamma TuRC-dependent microtubule nucleation and organization.