Dynein catch bond as a mediator of codependent bidirectional cellular transport

Abstract

Intracellular bidirectional transport of cargo on microtubule filaments is achieved by the collective action of oppositely directed dynein and kinesin motors. Experiments have found that in certain cases, inhibiting the activity of one type of motor results in an overall decline in the motility of the cellular cargo in both directions. This counterintuitive observation, referred to as the paradox of codependence, is inconsistent with the existing paradigm of a mechanistic tug of war between oppositely directed motors. Unlike kinesin motors, dynein motors exhibit catch bonding, wherein the unbinding rates of these motors decrease with increasing force on them. Incorporating this catch-bonding behavior of dyneins in a theoretical model, we show that the functional divergence of the two motor species manifests itself as an internal regulatory mechanism, and leads to codependent-transport behavior in biologically relevant regimes. Using analytical methods and stochastic simulations, we analyze the processivity characteristics and probability distribution of run times and pause times of transported cellular cargoes. We show that catch bonding can drastically alter the transport characteristics and also provide a plausible resolution of the paradox of codependence.