Paper

Microtubules form by progressively faster tubulin accretion, not by nucleation-elongation

Agard, David A, Rice, Luke, Moritz, Michelle

2020

Overview

Microtubules are dynamic polymers with fundamental roles in eukaryotes. Despite their importance, how new microtubules form is poorly understood. Textbooks focus on a nucleation-elongation mechanism in which monomers rapidly equilibrate with an unstable oligomer (nucleus) that limits the rate of polymer formation; once formed, the polymer elongates efficiently from this nucleus by monomer addition. Such models faithfully describe actin assembly, but fail to account for how more complex polymers like hollow microtubules assemble. Here we articulate a new model for microtubule formation that has three key features: microtubules initiate via rectangular, sheet-like structures which grow faster the larger they become; the dominant pathway proceeds via accretion, stepwise addition of longitudinal or lateral layers; a 'straightening penalty' to account for the energetic cost of Tubulin's curved-to-straight conformational transition. This model can quantitatively fit experimental assembly data, providing new insights into biochemical determinants and assembly pathways for microtubule nucleation. Competing Interest Statement The authors have declared no competing interest. Footnotes * To make the paper easier to follow/undrestand, we eliminated what had been the introductory figure discussing phenomenological scaling, and all panels of subsequent figures that relied on concepts from that introductory figure. To support the robustness of our claims, we analyzed a second, independently collected dataset. We made a number of other changes to text and figures with the goal of streamlining to improve readability, and to better explain some of the logic.

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: Actin / Elongation / Microtubules / Monomers / Nucleation / Polymerization / Self-assembly / Tubulin