Move in for the kill: motile microtubule regulators

Abstract

The stereotypical function of kinesin superfamily motors is to transport cargo along microtubules. However, some kinesins also shape the microtubule track by regulating microtubule assembly and disassembly. Recent work has shown that the kinesin-8 family of motors emerge as key regulators of cellular microtubule length. The studied kinesin-8s are highly processive motors that walk towards the microtubule plus-end. Once at plus-ends, they have complex effects on polymer dynamics; kinesin-8s either destabilize or stabilize microtubules, depending on the context. This review focuses on the mechanisms underlying kinesin-8-microtubule interactions and microtubule length control. We compare and contrast kinesin-8s with the other major microtubule-regulating kinesins (kinesin-4 and kinesin-13), to survey the current understanding of the diverse ways that kinesins control microtubule dynamics.

Figure 1. Interacting surfaces between kinesin motor domain and tubulin dimers

Structure of the kinesin-8/Kif18A motor domain – microtubule complex. Overview of the asymmetric unit of the 13 Å helical reconstruction shows the Kif18A motor domain bound to the α/β tubulin dimer. The kinesin-8-α tubulin contact mediated by loop L2 is highlighted in sky blue dotted circle. The motor-tubulin interface was depicted by a blue curve. This figure was adapted from [16].

Figure 2. A model for regulation of microtubule dynamics by kinesin-8

1. Kinesin-8s land on the lattice of a growing microtubule and walk processively towards the plus-end in a manner facilitated by its C-terminal microtubule-binding domain. 2. Kinesin-8s accumulate at the plus-end, slowing down microtubule growth and promoting catastrophe through a depolymerizing or capping mechanism. 3. During the shrinking phase, kinesin-8s at low concentrations inhibit microtubule shrinkage and promote rescue. The figure was adapted from [20].