Axonal Transport: A Constrained System

Abstract

Long-distance intracellular axonal transport is predominantly microtubule-based, and its impairment is linked to neurodegeneration. Here we review recent theoretical and experimental evidence that suggest that near the axon boundaries (walls), the effective viscosity can become large enough to impede cargo transport in small (but not large) caliber axons. Theoretical work suggests that this opposition to motion increases rapidly as the cargo approaches the wall. However, having parallel microtubules close enough together to enable a cargo to simultaneously engage motors on more than one microtubule dramatically enhances motor activity, and thus decreases the effects due to such opposition. Experimental evidence supports this hypothesis: in small caliber axons, microtubule density is higher, increasing the probability of having parallel microtubules close enough that they can be used simultaneously by motors on a cargo. For transport toward the minus-end of microtubules, e.g., toward the cell body in an axon, a recently discovered force adaptation system can also contribute to overcoming such opposition to motion.

Keywords: Axons; Dynein; Kinesin; Mitochondria; Molecular motors; Neurons; Pain; Theory; Transport.

Figure 1:

Cargos being hauled by motors along microtubules inside an axon. The spherical cargo has a radius of a in a cylindrical axon. The distance h is the closest approach of the cargo to the axon wall. The cargo has 2 motors. Two scenarios are shown. The top shows a single engaged motor hauling a cargo along a microtubule. The bottom shows both motors engaged in hauling the cargo. The key point of Wortman et al. is that the enhanced viscosity encountered by the cargo near the wall of the axon can be overcome by having multiple motors hauling the cargo along closely spaced parallel microtubules as shown at the bottom. Figure is from Wortman et al.