Modular assembly of the principal microtubule nucleator γ-TuRC

The gamma-tubulin ring complex (gamma-TuRC) is the principal microtubule nucleation template in vertebrates. Recent cryo-EM reconstructions visualized the intricate quaternary structure of the gamma-TuRC, containing more than thirty subunits, raising fundamental questions about gamma-TuRC assembly and the role of actin as an integral part of the complex. Here, we reveal the structural mechanism underlying modular gamma-TuRC assembly and identify a functional role of actin in microtubule nucleation. During gamma-TuRC assembly, a GCP6-stabilized core comprising GCP2-3-4-5-4-6 is expanded by stepwise recruitment, selective stabilization and conformational locking of four pre-formed GCP2-GCP3 units. Formation of the lumenal bridge specifies incorporation of the terminal GCP2-GCP3 unit and thereby leads to closure of the gamma-TuRC ring in a left-handed spiral configuration. Actin incorporation into the complex is not relevant for gamma-TuRC assembly and structural integrity, but determines gamma-TuRC geometry and is required for efficient microtubule nucleation and mitotic chromosome alignment in vivo. The human microtubule nucleator gamma-TuRC is composed of more than thirty subunits, including actin. Here the authors reveal the structural mechanism of modular gamma-TuRC assembly and show a functional role of actin in microtubule nucleation.

Automated summary

The study reveals the assembly mechanism of γ-TuRC and the functional role of actin in microtubule nucleation.