Smart motors and cargo steering drive kinesin-mediated selective transport

Abstract

Neurons are polarized cells, with dendrites and axons that require different complements of membrane proteins to fulfill their specialized functions. Membrane proteins are synthesized in the somatodendritic domain and delivered to their target membranes via long-range vesicle transport. Most anterograde vesicle transport is mediated by kinesin motors, but it is unclear how kinesins are targeted to axons or dendrites. Two main models have been proposed to explain kinesin selectivity. In the smart motor model, kinesin selectivity is conferred by a preference of the kinesin motor domain for specific subsets of microtubules. In the cargo steering model, kinesin selectivity is modulated by the vesicular cargo to which the motor is bound. We evaluate the evidence for both models and conclude that while the smart motor model may explain axonal selectivity, cargo steering is required for dendritic selectivity. Future work will determine the relative contributions of these models to polarized transport in living neurons.

Fig. 1.

Polarized transport in neurons. (A) Still image from a movie of an 8 DIV cultured hippocampal neuron expressing an axonal membrane protein, neuron-glia cell adhesion molecule (NgCAM; magenta), and a dendritic membrane protein, transferrin receptor (green). NgCAM vesicles are present in dendrites and enriched in the axon. Transferrin receptor vesicles are excluded from the axon. Scale bar: 10 μm. (B) Kymographs show the movement of NgCAM and transferrin receptor vesicles in axons and dendrites. Kymographs plot the maximum intensity at each position along the neurite (x-axis) as a function of time (y-axis). Diagonal lines indicate moving vesicles. Anterograde movement is represented by a positive slope; retrograde movement is represented by a negative slope. Contrast was inverted in kymographs so that bright vesicles appear dark.

Fig. 2.

A schematic illustrating the smart motor and cargo steering models. Each panel shows a vesicle and an associated kinesin. Arrows indicate the transport preference of that vesicle-kinesin pair into neurites. (A) In the smart motor model, the kinesin identity determines the transport behavior of the vesicle. Different kinesins are required for axon- and dendrite-selective transport. (B) In the cargo steering model, the molecular identity of the vesicle determines its transport behavior. The same kinesin can confer different transport behaviors, depending on the vesicle it is bound to.