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痉挛素在轴突生物学中的作用。

The Role of Spastin in Axon Biology.

作者信息

Costa Ana Catarina, Sousa Monica Mendes

机构信息

Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação Em Saúde (i3S), University of Porto, Porto, Portugal.

Graduate Program in Molecular and Cell Biology, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, Portugal.

出版信息

Front Cell Dev Biol. 2022 Jul 5;10:934522. doi: 10.3389/fcell.2022.934522. eCollection 2022.

DOI:10.3389/fcell.2022.934522
PMID:35865632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9294387/
Abstract

Neurons are highly polarized cells with elaborate shapes that allow them to perform their function. In neurons, microtubule organization-length, density, and dynamics-are essential for the establishment of polarity, growth, and transport. A mounting body of evidence shows that modulation of the microtubule cytoskeleton by microtubule-associated proteins fine tunes key aspects of neuronal cell biology. In this respect, microtubule severing enzymes-spastin, katanin and fidgetin-a group of microtubule-associated proteins that bind to and generate internal breaks in the microtubule lattice, are emerging as key modulators of the microtubule cytoskeleton in different model systems. In this review, we provide an integrative view on the latest research demonstrating the key role of spastin in neurons, specifically in the context of axonal cell biology. We focus on the function of spastin in the regulation of microtubule organization, and axonal transport, that underlie its importance in the intricate control of axon growth, branching and regeneration.

摘要

神经元是具有复杂形状的高度极化细胞,这些形状使它们能够执行其功能。在神经元中,微管组织(长度、密度和动力学)对于极性的建立、生长和运输至关重要。越来越多的证据表明,微管相关蛋白对微管细胞骨架的调节可微调神经元细胞生物学的关键方面。在这方面,微管切断酶(痉挛蛋白、katanin和fidgetin)是一组与微管晶格结合并在其中产生内部断裂的微管相关蛋白,在不同的模型系统中正在成为微管细胞骨架的关键调节因子。在本综述中,我们提供了最新研究的综合观点,证明了痉挛蛋白在神经元中的关键作用,特别是在轴突细胞生物学的背景下。我们专注于痉挛蛋白在微管组织调节和轴突运输中的功能,这些功能是其在轴突生长、分支和再生的复杂控制中重要性的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/97751ec0d9ad/fcell-10-934522-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/69d88f3df824/fcell-10-934522-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/87f9160fbbf8/fcell-10-934522-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/97751ec0d9ad/fcell-10-934522-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/69d88f3df824/fcell-10-934522-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/87f9160fbbf8/fcell-10-934522-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc5f/9294387/97751ec0d9ad/fcell-10-934522-g003.jpg

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本文引用的文献

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Phosphorylation of Spastin Promotes the Surface Delivery and Synaptic Function of AMPA Receptors.痉挛蛋白的磷酸化促进AMPA受体的表面转运和突触功能。
Front Cell Neurosci. 2022 Mar 28;16:809934. doi: 10.3389/fncel.2022.809934. eCollection 2022.
2
Mechanisms of microtubule organization in differentiated animal cells.分化动物细胞中微管组织的机制。
Nat Rev Mol Cell Biol. 2022 Aug;23(8):541-558. doi: 10.1038/s41580-022-00473-y. Epub 2022 Apr 5.
3
βIII-Tubulin Structural Domains Regulate Mitochondrial Network Architecture in an Isotype-Specific Manner.
内质网促进微管组织和区域特异性拆卸以执行区室化细胞清除。
bioRxiv. 2025 May 13:2025.05.08.652974. doi: 10.1101/2025.05.08.652974.
4
UCHL1-Mediated Spastin Degradation Regulates Microtubule Severing and Hippocampal Neurite Outgrowth.UCHL1介导的Spastin降解调控微管切断及海马神经突生长。
J Mol Neurosci. 2025 Apr 24;75(2):54. doi: 10.1007/s12031-025-02348-1.
5
Doublecortin restricts neuronal branching by regulating tubulin polyglutamylation.双皮质素通过调节微管蛋白多聚谷氨酰胺化来限制神经元分支。
Nat Commun. 2025 Feb 18;16(1):1749. doi: 10.1038/s41467-025-56951-2.
6
Targeting MDM2 affects spastin protein levels and functions: implications for HSP treatment.靶向MDM2会影响痉挛蛋白水平和功能:对遗传性痉挛性截瘫治疗的启示
Cell Death Discov. 2025 Feb 7;11(1):53. doi: 10.1038/s41420-025-02333-y.
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From spastic paraplegia to infantile neurodegenerative disorder: Expanding the phenotypic spectrum associated with biallelic SPAST variants.从痉挛性截瘫到婴儿神经退行性疾病:扩大与双等位基因SPAST变异相关的表型谱。
Eur J Neurol. 2025 Jan;32(1):e70025. doi: 10.1111/ene.70025.
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Biochim Biophys Acta Mol Cell Res. 2025 Feb;1872(2):119890. doi: 10.1016/j.bbamcr.2024.119890. Epub 2024 Dec 15.
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