Microtubule depolymerization by the kinesin-8 motor Kip3p: a mathematical model

TL;DR

This paper presents a mathematical model of kinesin-8 motor Kip3p that explains microtubule depolymerization, showing processive activity and length-dependent effects, aligning well with experimental data.

Contribution

The model integrates directional motility and destabilization to accurately reproduce microtubule length dynamics and depolymerization processivity.

Findings

Kinesin 8 depolymerizes processively, removing multiple tubulin dimers.

Length-dependent depolymerization occurs only in sufficiently short microtubules.

Depolymerization rate sensitivity depends on motor concentration.

Abstract

Proteins from the kinesin-8 family promote microtubule (MT) depolymerization, a process thought to be important for the control of microtubule length in living cells. In addition to this MT shortening activity, kinesin 8s are motors that show plus-end directed motility on MTs. Here we describe a simple model that incorporates directional motion and destabilization of the MT plus end by kinesin 8. Our model quantitatively reproduces the key features of length-vs-time traces for stabilized MTs in the presence of purified kinesin 8, including length-dependent depolymerization. Comparison of model predictions with experiments suggests that kinesin 8 depolymerizes processively, i.e., one motor can remove multiple tubulin dimers from a stabilized MT. Fluctuations in MT length as a function of time are related to depolymerization processivity. We have also determined the parameter regime in which the rate of MT depolymerization is length dependent: length-dependent depolymerization occurs only when MTs are sufficiently short; this crossover is sensitive to the bulk motor concentration.