Axonal transport cargo motor count versus average transport velocity: Is fast versus slow transport really single versus multiple motor transport?

AbstractCargos have been observed exhibiting a “stop-and-go” behavior (i.e. cargo “pause”), and it has generally been assumed that these multi-second pauses can be attributed to equally long pauses of cargo-bound motors during motor procession. We contend that a careful examination of the isolated microtubule experimental record does not support motor pauses. Rather, we believe that the data suggests that motor cargo complexes encounter an obstruction that prevents procession, eventually detach and reattach, with this obstructed-detach–reattach sequence being observed in axon as a “pause.” Based on this, along with our quantitative evidence-based contention that slow and fast axonal transport are actually single and multi-motor transport, we have developed a cargo level motor model capable of exhibiting the full range of slow to fast transport solely by changing the number of motors involved. This computational model derived using first-order kinetics is suitable for both kinesin and dynein and includes load-dependence as well as provision for motors encountering obstacles to procession. The model makes the following specific predictions: average distance from binding to obstruction is about 10μm; average motor maximum velocity is at least 6μm/s in axon; a minimum of 10 motors is required for the fastest fast transport while only one motor is required for slow transport; individual in-vivo cargo-attached motors may spend as little as 5% of their time processing along a microtubule with the remainder being spent either obstructed or unbound to a microtubule; and at least in the case of neurofilament transport, kinesin and dynein are largely not being in a “tug-of-war” competition