Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Freie Universität Berlin, Faculty of Biology, Chemistry, Berlin, Germany.
J Neurochem. 2021 Aug;158(3):589-602. doi: 10.1111/jnc.15287. Epub 2021 Jan 15.
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.
神经元因其精细的形态以及远端轴突与胞体之间的长距离，以及它们的长寿，给自噬和内溶酶体系统带来了特殊的挑战，这两个系统是有缺陷的蛋白质和细胞器周转的主要降解途径之一。自噬体通过将细胞质或细胞器货物包裹在其腔室中，然后与富含神经元胞体的降解溶酶体融合，从而隔离细胞质或细胞器货物，并参与逆行信号传递到胞体。内体主要参与内化或膜结合大分子的分拣、再循环或溶酶体周转，以维持轴突膜的稳态。溶酶体和多种溶酶体相关细胞器也具有非降解作用，例如在营养信号转导和突触形成中。近年来，人们开始揭示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。在这里，我们综述了这些细胞器在健康和疾病中的轴突中的定位、分布和越来越多的功能的现有认识，并概述了未来研究的前景。
