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.
Highlights
Eukaryotic cells are highly organized, and much of this organization is created and maintained by using active transport. Such transport utilizes a set of highways—the elongated polymers called microtubules (MTs)—combined with molecular motors—kinesin and dynein—that move along the highways
In this review we summarize recent theoretical work suggesting that transport of larger cargos in neurons may face significant obstacles to motion
Wortman et al.[12] hypothesized that axonal transport in small caliber axons can be hindered by the increased viscosity near the membrane; the existence of such opposition to motion was experimentally confirmed[21]
Summary
Eukaryotic cells are highly organized, and much of this organization is created and maintained by using active transport. Transport near axonal boundaries likely feels significant opposition to motion For the purposes of this review, we will confine our attention to transport in the axon where the microtubules are oriented with their plus ends away from the cell body[3,4].
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