Collective effects of yeast cytoplasmic dynein based microtubule transport

Abstract

Teams of cortically anchored dyneins pulling at microtubules (MTs) are known to be essential for aster, spindle and nuclear positioning during cell division and fertilization. While the single-molecule basis of dynein processivity is now better understood, the effect of increasing numbers of motors on transport is not clear. Here, we examine the collective transport properties of a Saccharomyces cerevisiae cytoplasmic dynein fragment, widely used as a minimal model, by a combination of quantitative MT gliding assays and stochastic simulations. We find both MT lengths and motor densities qualitatively affect the degree of randomness of MT transport. However, the directionality and velocity of MTs increase above a threshold number of motors (N) interacting with a filament. To better understand this behavior, we simulate a gliding assay based on a model of uniformly distributed immobilized motors transporting semi-flexible MTs. Each dynein dimer is modeled as an effective stochastic stepper with asymmetric force dependent detachment dynamics, based on single-molecule experiments. Simulations predict increasing numbers of motors (N) result in a threshold dependent transition in directionality and transport velocity and a monotonic decrease in effective diffusivity. Thus both experiment and theory show qualitative agreement in the emergence of coordination in transport above a threshold number of motor heads. We hypothesize that the phase-transition like property of this dynein could play a role in vivo during yeast mitosis, when this dynein localizes to the cortex and pulls astral MTs of increasing length, resulting in correct positioning and orientation of the nucleus at the bud-neck.