Local synaptic signaling enhances the stochastic transport of motor-driven cargo in neurons.

ABSTRACT

The tug-of-war model of motor-driven cargo transport is formulated as an intermittent trapping process. An immobile trap, representing the cellular machinery that sequesters a motor-driven cargo for eventual use, is located somewhere within a microtubule track. A particle representing a motor-driven cargo that moves randomly with a forward bias is introduced at the beginning of the track. The particle switches randomly between a fast moving phase and a slow moving phase. When in the slow moving phase, the particle can be captured by the trap. To account for the possibility that the particle avoids the trap, an absorbing boundary is placed at the end of the track. Two local signaling mechanisms--intended to improve the chances of capturing the target--are considered by allowing the trap to affect the tug-of-war parameters within a small region around itself. The first is based on a localized adenosine triphosphate (ATP) concentration gradient surrounding a synapse, and the second is based on a concentration of tau--a microtubule-associated protein involved in Alzheimer's disease--coating the microtubule near the synapse. It is shown that both mechanisms can lead to dramatic improvements in the capture probability, with a minimal increase in the mean capture time. The analysis also shows that tau can cause a cargo to undergo random oscillations, which could explain some experimental observations.