Three-Step Model for Polarized Sorting of KIF17 into Dendrites.
Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11]. Using live-cell imaging combined with inducible trafficking assays to directly probe KIF17 motor activity in living neurons, we found that the polarized sorting of KIF17 to dendrites is regulated in multiple steps. First, cargo binding of KIF17 relieves autoinhibition and initiates microtubule-based cargo transport. Second, KIF17 does not autonomously target dendrites, but enters the axon where the actin cytoskeleton at the axon initial segment (AIS) prevents KIF17 vesicles from moving further into the axon. Third, dynein-based motor activity is able to redirect KIF17-coupled cargoes into dendrites. We propose a three-step model for polarized targeting of KIF17, in which the collective function of multiple motor teams is required for proper dendritic sorting.
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Mariella A
MA
Franker
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Marta
M
Esteves da Silva
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Roderick P
RP
Tas
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Elena
E
Tortosa
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Yujie
Y
Cao
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Cátia P
CP
Frias
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Anne F J
AFJ
Janssen
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Phebe S
PS
Wulf
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
Lukas C
LC
Kapitein
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands. Electronic address: c.hoogenraad@uu.nl.
Casper C
CC
Hoogenraad
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D021381:Protein Transport; D051381:Rats
C485813:KIF17 protein, human; C000613396:KIF17 protein, rat; D016547:Kinesins
KIF17; autoinhibition; axon initial segment; dynein; motor protein; neuron; transport