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Polarity Sorting of Microtubules in the Axon
Journal article   Open access   Peer reviewed

Polarity Sorting of Microtubules in the Axon

Anand N Rao and Peter W Baas
Trends in neurosciences (Regular ed.), v 41(2), pp 77-88
Feb 2018
DOI: https://doi.org/10.1016/j.tins.2017.11.002
PMID: 29198454
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.tins.2017.11.002View
Published, Version of Record (VoR) Open

Abstract

microtubule axon microtubule polarity sorting microtubule sliding microtubule polarity orientation cytoplasmic dynein
A longstanding question in cellular neuroscience is how microtubules in the axon become organized with their plus ends out, a pattern starkly different from the mixed orientation of microtubules in vertebrate dendrites. Recent attention has focused on a mechanism called polarity sorting, in which microtubules of opposite orientation are spatially separated by molecular motor proteins. Here we discuss this mechanism, and conclude that microtubules are polarity sorted in the axon by cytoplasmic dynein but that additional factors are also needed. In particular, computational modeling and experimental evidence suggest that static crosslinking proteins are required to appropriately restrict microtubule movements so that polarity sorting by cytoplasmic dynein can occur in a manner unimpeded by other motor proteins. Almost all microtubules in the axon are uniformly oriented with their plus ends out, but the question remains of how this essential pattern is generated and preserved in the face of potential corruption. Polarity sorting of microtubules by molecular motor proteins has been posited as the mechanism by which the microtubule polarity pattern of the axon is established and preserved. In this mechanism, microtubules of opposite orientation are spatially separated so that minus-end-out microtubules are cleared from the axon by transport back to the cell body and plus-end-out microtubules are conveyed into and down the axon to populate its length. Cytoplasmic dynein is the principal motor protein that polarity sorts microtubules in the axon. A simple polarity-sorting mechanism is insufficient to explain microtubule organization in the axon, especially in light of other motors, such as kinesin-1, that may impede the dynein-based sorting process. Static microtubule crosslinking proteins may be the means by which microtubule movements are sufficiently restricted that dynein-based polarity sorting can be effective. Live-cell imaging and computer simulations have been instrumental in developing this model.

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