The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
The model of local axon homeostasis - explaining the role and regulation of microtubule bundles in axon maintenance and pathology
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局部轴突稳态模型 - 解释微管束在轴突维持和病理学中的作用和调节
DOI：
10.1101/577320
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Hahn I
中科院分区：
文献类型：
--
作者：
Hahn I
轴突是细长、电缆状、长达一米的神经元突起，连接我们的大脑和身体。尽管它们的形态具有挑战性，但它们通常需要在生物体的一生中得到维护。这使得它们成为衰老、损伤和神经退行性病变病理过程中的关键病变部位。轴突的形态和生理学在很大程度上取决于平行的微管束（MT），它们一直作为其结构支柱和维持生命的货物运输和细胞器动力学的高速公路。了解这些束是如何形成和维持的将为轴突生物学和病理学提供重要的解释。目前，人们对 MT 以及结合和调节它们的蛋白质了解很多，但对这些因子如何功能性整合以调节轴突生物学知之甚少。作为在分子机制与其细胞相关性之间架起桥梁的尝试，我们在此根据我们自己在果蝇中的实验以及主要来自脊椎动物/哺乳动物以及昆虫的已发表的数据来解释局部轴突稳态模型。线虫。该模型提出：(1) 运动蛋白驱动的运输和受限轴突空间动力学所施加的物理力是维持生命的必需品，但会导致 MT 束变得混乱。 (2) 为了平衡这种风险，不同类别的 MT 结合和调节蛋白共同作用，以维持和保护 MT 束作为必要的运输高速公路。这两个基本过程之间失去平衡可以解释轴突病的发生，特别是那些与 MT 调节蛋白、马达和运输缺陷相关的轴突病。考虑到这一点，我们希望更多的研究人员将 MT 纳入他们的工作中，从而增加我们破译支撑轴突生物学和病理学的复杂调控网络的机会。
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 inDrosophilaand published data primarily from vertebrates/mammals as well asC. 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.
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DOI：
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发表时间：
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期刊：
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影响因子：
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