Mixed microtubules steer dynein-driven cargo transport into dendrites.
BACKGROUND
To establish and maintain their polarized morphology, neurons employ active transport driven by molecular motors to sort cargo between axons and dendrites. However, the basic traffic rules governing polarized transport on neuronal microtubule arrays are unclear.


RESULTS
Here we show that the microtubule minus-end-directed motor dynein is required for the polarized targeting of dendrite-specific cargo, such as AMPA receptors. To directly examine how dynein motors contribute to polarized dendritic transport, we established a trafficking assay in hippocampal neurons to selectively probe specific motor protein activity. This revealed that, unlike kinesins, dynein motors drive cargo selectively into dendrites, governed by their mixed microtubule array. Moreover, axon-specific cargos, such as presynaptic vesicle protein synaptophysin, are redirected to dendrites by coupling to dynein motors. Quantitative modeling demonstrated that bidirectional dynein-driven transport on mixed microtubules provides an efficient mechanism to establish a stable density of continuously renewing vesicles in dendrites.


CONCLUSIONS
These results demonstrate a powerful approach to study specific motor protein activity inside living cells and imply a key role for dynein in dendritic transport. We propose that dynein establishes the initial sorting of dendritic cargo and additional motor proteins assist in subsequent delivery.
Department of Neuroscience, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Lukas C
LC
Kapitein
Max A
MA
Schlager
Marijn
M
Kuijpers
Phebe S
PS
Wulf
Myrrhe
M
van Spronsen
Frederick C
FC
MacKintosh
Casper C
CC
Hoogenraad
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D019556:COS Cells; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D020675:Peroxisomes / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
D018091:Receptors, AMPA; D016708:Synaptophysin; D004398:Dyneins; D016547:Kinesins