Smart motors and cargo steering drive kinesin-mediated selective transport

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. •Neuronal polarity is maintained by selective vesicle transport to axons or dendrites.•Kinesin family members are microtubule-based motors that mediate vesicle transport.•We review the two models—smart motors and cargo steering—that have been proposed to explain kinesin selectivity.