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Τετάρτη 14 Ιουνίου 2017

Cytoplasmic Dynein Transports Axonal Microtubules in a Polarity-Sorting Manner

Publication date: 13 June 2017
Source:Cell Reports, Volume 19, Issue 11
Author(s): Anand N. Rao, Ankita Patil, Mark M. Black, Erin M. Craig, Kenneth A. Myers, Howard T. Yeung, Peter W. Baas
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.

Graphical abstract

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Teaser

Rao et al. show that the plus-end-out microtubule polarity pattern of the axon can be explained by a polarity-sorting mechanism driven by cytoplasmic dynein, together with the participation of other players that include an opposing motor and a cross-linker protein.


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