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Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner

Rao, Anand N.
Patil, Ankita
Black, Mark M.
Craig, Erin M.
Myers, Kenneth A.
Yeung, Howard T.
Baas, Peter W.
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Journal article
Date
2017-06-13
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Anatomy and Cell Biology
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DOI
https://doi.org/10.1016/j.celrep.2017.05.064
Abstract
Axonal microtubules are predominantly organized into a plus-end-out pattern. Here, we tested both experimentally and with computational modeling whether a motor-based polarity-sorting mechanism can explain this microtubule pattern. The posited mechanism centers on cytoplasmic dynein transporting plus-end-out and minus-end-out microtubules into and out of the axon, respectively. When cytoplasmic dynein was acutely inhibited, the bi-directional transport of microtubules in the axon was disrupted in both directions, after which minus-end-out microtubules accumulated in the axon over time. Computational modeling revealed that dynein-mediated transport of microtubules can establish and preserve a predominantly plus-end-out microtubule pattern as per the details of the experimental findings, but only if a kinesin motor and a static cross-linker protein are also at play. Consistent with the predictions of the model, partial depletion of TRIM46, a protein that cross-links axonal microtubules in a manner that influences their polarity orientation, leads to an increase in microtubule transport.
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Cell Press
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Cell Reports, Vol. 19, Iss. 11
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