title: Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites.
abstract: 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.
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lipka
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Kapitein
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.affiliation: Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands c.hoogenraad@uu.nl.
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D001692:Biological Transport; D003712:Dendrites / Q000378:metabolism*; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C490575:Kif1a protein, rat; D000089742:Doublecortin-Like Kinases; C485526:Dclk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins
keywords: dendrite; doublecortin; kinesin; neuron; polarity