Polarized Targeting

We are interested in the fundamental question of how proteins are targeted to either the axon or the dendrites. Vesicles carrying transmembrane proteins are transported to the axonal or somatodendritic domains in distinct vesicles that are propelled by distinct kinesin isoforms. The proteins are likely sorted into distinct vesicles in much the same manner as are apical and basolateral proteins in epithelial cells. However, the second step of the process, during which vesicles carrying either axonal or dendritic proteins associate with microtubules projecting to the appropriate compartment, is completely mysterious.

If different kinesin isofororms could distinguish between axonal and dendritic microtubules, it would explain how specificity could be achieved in the second step of targeting. However, several studies have shown that kinesins cannot autonomously distinguish between axonal and dendritic microtubules. We have recently discovered a novel mechanism that could account for how this second step works in both axonal and dendritic targeting. As we are currently in the process of publishing this work, it would be premature to post it here, but stay tuned.