Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites

In neurons, the polarized distribution of vesicles and other cellular materials is established through molecular motors that steer selective transport between axons and dendrites. It is currently unclear whether interactions between kinesin motors and microtubule‐binding proteins can steer polarized transport. By screening all 45 kinesin family members, we systematically addressed which kinesin motors can translocate cargo in living cells and drive polarized transport in hippocampal neurons. While the majority of kinesin motors transport cargo selectively into axons, we identified five members of the kinesin‐3 (KIF1) and kinesin‐4 (KIF21) subfamily that can also target dendrites. We found that microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) labels a subset of dendritic microtubules and is required for KIF1‐dependent dense‐core vesicles (DCVs) trafficking into dendrites and dendrite development. Our study demonstrates that microtubule‐binding proteins can provide local signals for specific kinesin motors to drive polarized cargo transport. Synopsis While kinesin motors selectively move into axons, kinesin‐3 and kinesin‐4 can also target dendrites. Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) provides local cues to steer polarized movement of kinesin‐3 into dendrites. Twenty‐three members of the kinesin subfamily are able to transport cargo in living cells. Kinesin‐3 (KIF1) and kinesin‐4 (KIF21) family members target both axon and dendrites. DCLK1 associates with a specific subset of microtubules in dendrites. DCLK1 is required for KIF1‐mediated dense‐core vesicle trafficking into dendrites. Graphical Abstract While kinesin motors selectively move into axons, kinesin‐3 and kinesin‐4 can also target dendrites. Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) provides local cues to steer polarized movement of kinesin‐3 into dendrites.