Differential Regulation of Dynein and Kinesin Motor Proteins by Tau

TLDR

Dynein and kinesin move cargoes toward opposite ends of microtubules, and in neurons these tracks are densely coated with MAPs such as tau that the motors frequently encounter. The study aimed to determine how tau affects dynein and kinesin motility by performing single‑molecule assays on tau‑decorated microtubules. Single‑molecule assays of motor proteins moving along tau‑decorated microtubules were conducted. Dynein reversed direction while kinesin detached at tau patches, with kinesin inhibited at roughly one‑tenth the tau concentration needed for dynein; tau’s microtubule‑binding domain alone sufficed to inhibit motor activity, indicating MAPs can spatially regulate axonal transport.

Abstract

Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein and kinesin motility, we conducted single-molecule studies of motor proteins moving along tau-decorated microtubules. Dynein tended to reverse direction, whereas kinesin tended to detach at patches of bound tau. Kinesin was inhibited at about a tenth of the tau concentration that inhibited dynein, and the microtubule-binding domain of tau was sufficient to inhibit motor activity. The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport.