Interplay between velocity and travel distance of kinesin-based transport in the presence of tau

TL;DR

This study reveals that tau protein affects kinesin transport by decreasing single-kinesin velocity, which paradoxically can increase overall travel distance in multiple-kinesin systems, highlighting complex transport regulation mechanisms.

Contribution

It demonstrates that reducing single-kinesin velocity can upregulate travel distance despite tau inhibition, offering new insights into transport regulation in cells.

Findings

Multiple-kinesin travel distance increases despite tau presence.

Tau reduces single-kinesin velocity and cargo velocity.

Simulations show velocity reduction underlies increased travel distance.

Abstract

Although the disease-relevant microtubule-associated protein tau is known to severely inhibit kinesin-based transport in vitro, the potential mechanisms for reversing this detrimental effect to maintain healthy transport in cells remain unknown. Here we report the unambiguous upregulation of multiple-kinesin travel distance despite the presence of tau, via decreased single-kinesin velocity. Interestingly, the presence of tau also modestly reduced cargo velocity in multiple-kinesin transport, and our stochastic simulations indicate that the tau-mediated reduction in single-kinesin travel underlies this observation. Taken together, our observations highlight a nontrivial interplay between velocity and travel distance for kinesin transport, and suggest that single-kinesin velocity is a promising experimental handle for tuning the effect of tau on multiple-kinesin travel distance.