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

Abstract

SummaryThe 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 c-tubulin, an essential protein that assembles into multi-subunit complexes and is found in all eukaryotic organisms. However, the way in which c-tubulin complexes are regulated and how this affects nucleation and, potentially, microtubule behavior, is poorly understood. c-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 c-tubulin ring complexes (cTuRCs) are composed of c-tubulin and the c-tubulin complex components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein family. Recent work has identified additional unrelated cTuRC subunits, as well as a large number of more transient cTuRC interactors. In this Commentary, we discuss the regulation of cTuRC-dependent microtubule nucleation as a key mechanism of microtubule organization. Specifically, we focus on the regulatory roles of the cTuRC subunits and interactors and present an overview of other mechanisms that regulate cTuRC-dependent microtubule nucleation and organization.

The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation

“…MEL-28, however, does not associate with these two proteins, but interacts with gTuRC and the Nup107-160 complex. MEL-28, TPX2 and HURP may be involved in different steps of RanGTPdependent microtubule nucleation 23 . TPX2 depletion induces the most severe defects in Ran-induced microtubule nucleation 3 , whereas MEL-28 depletion results in the most severe defects in sperm spindle assembly.…”

The Centrosome and Its Duplication Cycle

“…Many other eukaryotes generate a larger g-tubulin complex, the g-tubulin ring complex (g-TuRC) that contains Spc97/Spc98 orthologs and three further molecules that share the Grip motifs of Spc97 and Spc98 (GCP2-GCP6 [GCP2 and GCP3 being orthologous to Spc97 and Spc98, respectively]) alongside two or three additional components (Kollman et al 2011;Teixido-Travesa et al 2012). As its name suggests the g-TuRC is a lock-washer-shaped ring in which the positioning of 13 g-tubulin molecules serves as a template to recruit 13 ab-tubulin heterodimers that seed the nucleation of 13 protofilament microtubules (Moritz et al 1995;Kollman et al 2011;Teixido-Travesa et al 2012). The conserved g-TuSC is Y shaped with Spc97/GCP2 and Spc98/GCP3 at the base of two g-tubulin arms (Kollman et al 2008).…”

Microtubule Nucleation in Mouse Bone Marrow–Derived Mast Cells Is Regulated by the Concerted Action of GIT1/βPIX Proteins and Calcium

“…Thus, kinases associated with GIT1/bPIX may phosphorylate components of gTuRC to promote the assembly of the complex, or they may regulate the association or activity of NEDD1/ GCP-WD, the attachment factor that lies most proximal to gTuRC and is required for the centrosomal recruitment of gTuRC (53). Alternatively, GIT1/bPIX may indirectly affect this process by regulating the assembly of the pericentriolar matrix or the activity of a centrosomal protein(s) required for the anchorage of gTuRCs (54).…”