The gamma‐tubulin ring complex: Deciphering the molecular organization and assembly mechanism of a major vertebrate microtubule nucleator

Abstract

Microtubules are protein cylinders with functions in cell motility, signal sensing, cell organization, intracellular transport, and chromosome segregation. One of the key properties of microtubules is their dynamic architecture, allowing them to grow and shrink in length by adding or removing copies of their basic subunit, the heterodimer αβ-tubulin. In higher eukaryotes, de novo assembly of microtubules from αβ-tubulin is initiated by a 2 MDa multi-subunit complex, the gamma-tubulin ring complex (γ-TuRC). For many years, the structure of the γ-TuRC and the function of its subunits remained enigmatic, although structural data from the much simpler yeast counterpart, the γ-tubulin small complex (γ-TuSC), were available. Two recent breakthroughs in the field, high-resolution structural analysis and recombinant reconstitution of the complex, have revolutionized our knowledge about the architecture and function of the γ-TuRC and will form the basis for addressing outstanding questions about biogenesis and regulation of this essential microtubule organizer. K E Y W O R D Sgamma-tubulin ring complex, gamma-tubulin small complex, gamma-tubulin, microtubule nucleation, microtubules, recombinant gamma-tubulin ring complex Abbreviations: AAA+, adenosine triphosphatases associated with various cellular activities;Arps, actin-related proteins; CDK5RAP2, CDK5 regulatory subunit-associated protein 2; CEP192, centrosomal protein of 192 kDa; ch-TOG, colonic hepatic tumor-overexpressed gene; CM1, centrosomin motif 1; GCP, γ-TuC component protein; γ-TuCs, γ-tubulin complexes; γ-TuRC, γ-tubulin ring complex; γ-TuSC, γ-tubulin small complex; GRIP1/2, γ-tubulin ring protein 1/2; HSP90, heat shock protein 90; INO80, inositol-requiring mutant 80 complex; MZT1/2, mitotic spindle organizing protein 1/2; NEDD1, neural precursor cell expressed, developmentally down-regulated 1; NME7, nucleotide diphosphate kinase 7; PCM, pericentriolar material; PIH1D1, PIH1 domain containing 1; R2TP, Rvb1-Rvb2-Tah1-Pih1; RPAP3, RNA polymerase II associated protein 3; RUVBL1/2, RuvB-like 1/2; SPB, spindle pole body; SWR1, SWI2/SNF2-related 1 complex; XMAP215, Xenopus microtubule assembly protein with 215 kDThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Changes in seam number and location induce holes within microtubules assembled from porcine brain tubulin and in Xenopus egg cytoplasmic extracts

“…Therefore, our results suggest that the formation of heterogeneous microtubule lattices is an intrinsic property of tubulin polymerization, which is firmly regulated in cells. One key regulatory factor could be the γ-tubulin ring complex (γTuRC), which imposes the 13 protofilament organization to a nascent microtubule (Böhler et al, 2021). But how this structure is preserved during microtubule elongation remains unclear, especially if one considers a two-dimensional assembly process where the lattice can vary in terms of protofilament number, helix-start number, or lattice type during elongation.…”

Two Important Anticancer Mechanisms of Natural and Synthetic Chalcones

“…These dynamic structures are constantly elongated or shortened in all phases of cell cycle by adding or removing tubulin heterodimers from the ends of microtubules [ 199 , 200 , 201 , 202 ]. The assembly of protofilaments to microtubules is done spontaneously, with a number of protofilaments between 9 and 16, resulting in microtubules with different diameters [ 203 ]. It is known that the organization of microtubules changes significantly during the cell cycle.…”

Transition of human γ-tubulin ring complex into a closed conformation during microtubule nucleation

“…Recent cryo-electron microscopy (cryo-EM) structures of human and Xenopus gTuRC revealed that two adjacent GCP2/3 pairs are replaced by a GCP4/5 pair and a GCP4/6 pair, and that a "luminal bridge" is positioned inside the cone (27)(28)(29)(30). This bridge contains an actin-like molecule and two copies of mitoticspindle organizing protein 1 (MZT1) and the N-terminal extensions (NTEs) of one GCP3 and GCP6, forming MZT1/3NTE and MZT1/6NTE modules (31), which have been proposed to be important for complex assembly and stability (32)(33)(34). The function of the actin-like molecule in the gTuRC is less understood, much like the unclear role of an "end protrusion" that extends from the last GCP3 on the outside of the complex, possibly representing another MZT1-like/ NTE module (28)(29)(30)(31)35).…”