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

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 o...

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Main Authors: Ines Hahn, André Voelzmann, Yu-Ting Liew, Beatriz Costa-Gomes, Andreas Prokop
Format: Article
Language:English
Published: BMC 2019-11-01
Series:Neural Development
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13064-019-0134-0
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spelling doaj-cc49e45a31e041a78115bd47689071b92020-11-25T03:56:59ZengBMCNeural Development1749-81042019-11-0114112810.1186/s13064-019-0134-0The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathologyInes Hahn0André Voelzmann1Yu-Ting Liew2Beatriz Costa-Gomes3Andreas Prokop4Manchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, School of BiologyManchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, School of BiologyManchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, School of BiologyManchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, School of BiologyManchester Academic Health Science Centre, Faculty of Biology, Medicine and Health, The University of Manchester, School of BiologyAbstract 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.http://link.springer.com/article/10.1186/s13064-019-0134-0Drosophilaneurodegenerationaxonsactincytoskeletonmicrotubules
collection DOAJ
language English
format Article
sources DOAJ
author Ines Hahn
André Voelzmann
Yu-Ting Liew
Beatriz Costa-Gomes
Andreas Prokop
spellingShingle Ines Hahn
André Voelzmann
Yu-Ting Liew
Beatriz Costa-Gomes
Andreas Prokop
The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
Neural Development
Drosophila
neurodegeneration
axons
actin
cytoskeleton
microtubules
author_facet Ines Hahn
André Voelzmann
Yu-Ting Liew
Beatriz Costa-Gomes
Andreas Prokop
author_sort Ines Hahn
title The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
title_short The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
title_full The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
title_fullStr The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
title_full_unstemmed The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
title_sort model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
publisher BMC
series Neural Development
issn 1749-8104
publishDate 2019-11-01
description 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.
topic Drosophila
neurodegeneration
axons
actin
cytoskeleton
microtubules
url http://link.springer.com/article/10.1186/s13064-019-0134-0
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