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The model of local axon homeostasis - Explaining the role and regulation of microtubule bundles in axon maintenance and pathology

Hahn, Ines; Voelzmann, André; Liew, Yu Ting; Costa-Gomes, Beatriz; Prokop, Andreas

Authors

Ines Hahn

Yu Ting Liew

Beatriz Costa-Gomes

Andreas Prokop



Abstract

Axons are the slender, cable-like, up to meter-long projections of neurons that electrically wire our brains and bodies. In spite of their challenging morphology, they usually need to be maintained for an organism's lifetime. This makes them key lesion sites in pathological processes of ageing, injury and neurodegeneration. The morphology and physiology of axons crucially depends on the parallel bundles of microtubules (MTs), running all along to serve as their structural backbones and highways for life-sustaining cargo transport and organelle dynamics. Understanding how these bundles are formed and then maintained will provide important explanations for axon biology and pathology. Currently, much is known about MTs and the proteins that bind and regulate them, but very little about how these factors functionally integrate to regulate axon biology. As an attempt to bridge between molecular mechanisms and their cellular relevance, we explain here the model of local axon homeostasis, based on our own experiments in Drosophila and published data primarily from vertebrates/mammals as well as C. elegans. The model proposes that (1) the physical forces imposed by motor protein-driven transport and dynamics in the confined axonal space, are a life-sustaining necessity, but pose a strong bias for MT bundles to become disorganised. (2) To counterbalance this risk, MT-binding and -regulating proteins of different classes work together to maintain and protect MT bundles as necessary transport highways. Loss of balance between these two fundamental processes can explain the development of axonopathies, in particular those linking to MT-regulating proteins, motors and transport defects. With this perspective in mind, we hope that more researchers incorporate MTs into their work, thus enhancing our chances of deciphering the complex regulatory networks that underpin axon biology and pathology.

Citation

Hahn, I., Voelzmann, A., Liew, Y. T., Costa-Gomes, B., & Prokop, A. (2019). The model of local axon homeostasis - Explaining the role and regulation of microtubule bundles in axon maintenance and pathology. Neural Development, 14(1), Article 11. https://doi.org/10.1186/s13064-019-0134-0

Journal Article Type Review
Acceptance Date Oct 2, 2019
Online Publication Date Nov 9, 2019
Publication Date Nov 9, 2019
Deposit Date Feb 8, 2024
Publicly Available Date Feb 14, 2024
Journal Neural Development
Electronic ISSN 1749-8104
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 14
Issue 1
Article Number 11
DOI https://doi.org/10.1186/s13064-019-0134-0
Keywords Drosophila; Neurodegeneration; Axons; Actin; Cytoskeleton; Microtubules
Public URL https://hull-repository.worktribe.com/output/4371846

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
© The Author(s). 2019.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.




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