Mixed Microtubules Steer Dynein-Driven Cargo Transport into Dendrites

• Published in: Current biology 2010-02, Vol.20 (4), p.290-299
• Main Authors: Kapitein, Lukas C., Schlager, Max A., Kuijpers, Marijn, Wulf, Phebe S., van Spronsen, Myrrhe, MacKintosh, Frederick C., Hoogenraad, Casper C.
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport, Active - physiology; CELLBIO; Cercopithecus aethiops; COS Cells; Dendrites - metabolism; Dyneins - metabolism; Hippocampus - cytology; Immunohistochemistry; Kinesin - metabolism; Microtubules - metabolism; Models, Biological; MOLNEURO; Peroxisomes - metabolism; Receptors, AMPA - metabolism; Synaptophysin - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2009.12.052

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. 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. 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. [Display omitted] ► A new toolbox to probe specific motor proteins inside neurons is introduced ► Dynein selectively targets cargo to dendrites, whereas kinesins mainly target axons ► Dynein's dendritic dynamics is governed by the mixed orientations of microtubules ► Dynein inhibition disrupts the polarized sorting of AMPA receptors