The axonal endolysosomal and autophagic systems
The axonal endolysosomal and autophagic systems
复制标题
DOI：
10.1111/jnc.15287
复制
发表时间：
2020-12
影响因子：
4.7
通讯作者：
M. Kuijpers;D. Azarnia Tehran;V. Haucke;Tolga Soykan
中科院分区：
文献类型：
--
作者：
M. Kuijpers;D. Azarnia Tehran;V. Haucke;Tolga Soykan
神经元由于其复杂的形态和远端轴突与体细胞之间的长距离以及它们的寿命，对自噬和内溶酶体系统构成了特殊的挑战，这是缺陷蛋白质和细胞器翻转的两种主要降解途径。自噬体在与神经元体细胞中富集的降解溶酶体融合之前，通过将细胞质或细胞器货物吞噬到其腔内，并参与向体细胞的逆行信号传导。内体主要参与内化或膜结合大分子的分类、再循环或溶酶体周转，以维持轴突膜的稳态。溶酶体和多种与溶酶体相关的细胞器也具有非降解作用，例如，在营养信号传导和突触形成中。近年来，人们开始研究神经元中自噬和内溶酶体系统的独特组织，特别是它们在轴突中的作用。在此，我们回顾了目前对轴突中这些细胞器在健康和疾病中的定位、分布和不断增长的功能列表的理解，并概述了未来研究的前景。
Neurons, because of their elaborate morphology and the long distances between distal axons and the soma as well as their longevity, pose special challenges to autophagy and to the endolysosomal system, two of the main degradative routes for turnover of defective proteins and organelles. Autophagosomes sequester cytoplasmic or organellar cargos by engulfing them into their lumen before fusion with degradative lysosomes enriched in neuronal somata and participate in retrograde signaling to the soma. Endosomes are mainly involved in the sorting, recycling, or lysosomal turnover of internalized or membrane‐bound macromolecules to maintain axonal membrane homeostasis. Lysosomes and the multiple shades of lysosome‐related organelles also serve non‐degradative roles, for example, in nutrient signaling and in synapse formation. Recent years have begun to shed light on the distinctive organization of the autophagy and endolysosomal systems in neurons, in particular their roles in axons. We review here our current understanding of the localization, distribution, and growing list of functions of these organelles in the axon in health and disease and outline perspectives for future research.