Microtubule nucleation by γ-tubulin complexes

Abstract

Microtubule nucleation is controlled by the γ-tubulin ring complex (γTuRC) and related γ-tubulin complexes, providing spatial and temporal control over the initiation of microtubule growth. Recent structural work has shed light on the mechanism of γTuRC-based microtubule nucleation, confirming the long-standing hypothesis that it functions as a microtubule template. Crystallographic analysis of the first non-γ-tubulin γTuRC component (GCP4) has resulted in a new appreciation of the relationships among all γTuRC proteins, leading to a refined model of their organization and function. The structures have also suggested an unexpected mechanism for regulating γTuRC activity via conformational modulation of the complex component GCP3. New experiments on γTuRC localization extend these insights, suggesting a direct link between attachment at specific cellular sites and activation.

The Centrosome and Its Duplication Cycle

“…In turn, Nud1 recruits both the mitotic exit network (MEN) that regulates cell-cycle events at the end of the cycle (see the section on signaling from poles below) and the g-tubulin complex receptor Spc72 (Knop and Schiebel 1998;Gruneberg et al 2000). g-Tubulin recruits ab-tubulin heterodimers to nucleate microtubules at the spindle poles of all eukaryotes (Kollman et al 2011;TeixidoTravesa et al 2012). Comprehensive molecular genetic analysis in budding yeast led to the characterization of the first g-tubulin complex, the g-tubulin small complex (g-TuSC) (Geissler et al 1996;; Schiebel 1997, 1998).…”

Microtubule nucleation and organization in dendrites

“…33 g-TuRC is central to the majority of cellular microtubule nucleation processes, and it is localized and activated to create microtubule organizing centers within the cell. 23,24 Loss of g-tubulin or g-TuRC factors reduces microtubule polymerization frequency in both dendrites and axons of hippocampal neuron cultures and in terminal dendrite branches of Drosophila class IV sensory neurons. 34,35 Pre-existing microtubule fragments can also act as seeds.…”

“…32 The microtubule seed is commonly provided by a template of g-tubulin and associated proteins in the g-tubulin ring complex (g-TuRC). 23,24 g-tubulin provides the initiation template for polymerization. 33 g-TuRC is central to the majority of cellular microtubule nucleation processes, and it is localized and activated to create microtubule organizing centers within the cell.…”

“…They are constructed from heterodimers of a-and b-tubulin that attach in a head-to-tail manner, pack laterally, usually with 13 heterodimers (13 protofilaments) per cross section, and fold to form a tube. 23,24 In relatively thin cellular processes such as dendrites the length of microtubules exceeds the diameter of the cell, and therefore microtubules are necessarily orientated either plus-end distal and anterograde polymerizing (away from the cell body), or minus-end distal and retrograde polymerizing (toward the cell body). 25 Dendrites contain both possible polarities, while microtubules in the mature axon are predominantly oriented in a plus-end distal orientation.…”

Organization of early frog embryos by chemical waves emanating from centrosomes

“…Cytoplasmic dynein is thought to exert outward force on astral microtubules [3], so it is possible that minus ends are released and glide outwards (figure 3g). We have so far assumed the minus ends formed away from centrosomes are stable, presumably capped by g-tubulin ring complex [75,76] or the CAMSAP/Patronin family of proteins [77 -79], but they may well be free to depolymerize. The reaction -diffusion model presented above predicts that the aster expansion rate increases indefinitely with nucleation rate, but this seems physically implausible given that microtubules polymerize at finite speed.…”