Structural analysis of the role of TPX2 in branching microtubule nucleation

Author:

Alfaro-Aco Raymundo1ORCID,Thawani Akanksha2,Petry Sabine1ORCID

Affiliation:

1. Department of Molecular Biology, Princeton University, Princeton, NJ 08544

2. Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544

Abstract

The mitotic spindle consists of microtubules (MTs), which are nucleated by the γ-tubulin ring complex (γ-TuRC). How the γ-TuRC gets activated at the right time and location remains elusive. Recently, it was uncovered that MTs nucleate from preexisting MTs within the mitotic spindle, which requires the protein TPX2, but the mechanism basis for TPX2 action is unknown. Here, we investigate the role of TPX2 in branching MT nucleation. We establish the domain organization of Xenopus laevis TPX2 and define the minimal TPX2 version that stimulates branching MT nucleation, which we find is unrelated to TPX2’s ability to nucleate MTs in vitro. Several domains of TPX2 contribute to its MT-binding and bundling activities. However, the property necessary for TPX2 to induce branching MT nucleation is contained within newly identified γ-TuRC nucleation activator motifs. Separation-of-function mutations leave the binding of TPX2 to γ-TuRC intact, whereas branching MT nucleation is abolished, suggesting that TPX2 may activate γ-TuRC to promote branching MT nucleation.

Funder

National Institutes of Health

National Institute of General Medical Sciences

Sidney Kimmel Foundation

David and Lucile Packard Foundation

Howard Hughes Medical Institute

National Science Foundation

Publisher

Rockefeller University Press

Subject

Cell Biology

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