Activation of mammalian cytoplasmic dynein in multimotor motility assays

Abstract

Long-range intracellular transport is facilitated by motor proteins, such as kinesin-1 and cytoplasmic dynein, moving along microtubules (MTs). These motors often work in teams for the transport of various intracellular cargos. Although transport by multiple kinesin-1 motors has been studied extensively in the past, collective effects of cytoplasmic dynein are less well understood. On the level of single molecules, mammalian cytoplasmic dynein is not active in the absence of dynactin and adaptor proteins. However, when assembled into a team bound to the same cargo, processive motility has been observed. The underlying mechanism of this activation is not known. Here, we found that in MT gliding motility assays the gliding velocity increased with dynein surface density and MT length. Developing a mathematical model based on single-molecule parameters, we were able to simulate the observed behavior. Integral to our model is the usage of an activation term, which describes a mechanical activation of individual dynein motors when being stretched by other motors. We hypothesize that this activation is similar to the activation of single dynein motors by dynactin and adaptor proteins.This article has an associated First Person interview with the first author of the paper.

Keywords: Gliding motility assay; Mammalian cytoplasmic dynein; Stochastic modeling.