Force transduction by the microtubule-bound Dam1 ring

TL;DR

This paper analyzes computational models of the Dam1 ring's force transduction mechanism during microtubule depolymerization, proposing experimental tests to distinguish between different theoretical models of its attachment.

Contribution

It identifies two distinct mechanisms in existing models and suggests experimental approaches to determine which mechanism is correct.

Findings

Two mechanisms: physical prevention by splayed protofilaments and attractive binding.

Proposed experiments include altering diffusion constants and applying time-varying loads.

Guidelines for experimental validation of the models.

Abstract

The coupling between the depolymerization of microtubules (MTs) and the motion of the Dam1 ring complex is now thought to play an important role in the generation of forces during mitosis. Our current understanding of this motion is based on a number of detailed computational models. Although these models realize possible mechanisms for force transduction, they can be extended by variation of any of a large number of poorly measured parameters and there is no clear strategy for determining how they might be distinguished experimentally. Here we seek to identify and analyze two distinct mechanisms present in the computational models. In the first the splayed protofilaments at the end of the depolymerizing MT physically prevent the Dam1 ring from falling off the end, in the other an attractive binding secures the ring to the microtubule. Based on this analysis, we discuss how to distinguish between competing models that seek to explain how the Dam1 ring stays on the MT. We propose novel experimental approaches that could resolve these models for the first time, either by changing the diffusion constant of the Dam1 ring (e.g., by tethering a long polymer to it) or by using a time varying load.