突触前自噬相关过程的组织

IF 2.8 4区 医学 Q2 NEUROSCIENCES
Frontiers in Synaptic Neuroscience Pub Date : 2022-03-17 eCollection Date: 2022-01-01 DOI:10.3389/fnsyn.2022.829354
Eckart D Gundelfinger, Anna Karpova, Rainer Pielot, Craig C Garner, Michael R Kreutz
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引用次数: 0

摘要

大脑突触对其蛋白质机制的质量控制提出了特殊的挑战,因为它们远离神经元胞体,表现出很高的可塑性适应潜力,并且有很高的能量需求来完成其生理任务。这尤其适用于突触前部分,其中神经递质从突触小泡中释放,而突触小泡又必须在复杂的膜运输循环中循环和再填充。去除过时和受损蛋白质的途径包括在细胞质中作用的泛素-蛋白酶体系统,以及膜相关的内溶酶体和自噬系统。在这里,我们专注于后一个系统,并回顾已知的突触前自噬和内溶体过程的空间组织。我们提供了这些降解系统的哪些成分被发现存在于突触前发作中,以及它们可能锚定在突触前器的位置。据报道,我们鉴定了三种突触前结构,它们与基于膜的蛋白质降解途径的已知成分相互作用,因此可以作为对接站。这些是(i)活性区细胞基质的支架蛋白,如巴松管或Clarinet,(ii)主要定位于活性区周围的内吞机制,以及(iii)突触小泡。最后,我们概述了突触前自噬货物是如何被标记和募集的,以及哪些细胞机制可能控制突触前的膜相关蛋白周转。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Organization of Presynaptic Autophagy-Related Processes.

Brain synapses pose special challenges on the quality control of their protein machineries as they are far away from the neuronal soma, display a high potential for plastic adaptation and have a high energy demand to fulfill their physiological tasks. This applies in particular to the presynaptic part where neurotransmitter is released from synaptic vesicles, which in turn have to be recycled and refilled in a complex membrane trafficking cycle. Pathways to remove outdated and damaged proteins include the ubiquitin-proteasome system acting in the cytoplasm as well as membrane-associated endolysosomal and the autophagy systems. Here we focus on the latter systems and review what is known about the spatial organization of autophagy and endolysomal processes within the presynapse. We provide an inventory of which components of these degradative systems were found to be present in presynaptic boutons and where they might be anchored to the presynaptic apparatus. We identify three presynaptic structures reported to interact with known constituents of membrane-based protein-degradation pathways and therefore may serve as docking stations. These are (i) scaffolding proteins of the cytomatrix at the active zone, such as Bassoon or Clarinet, (ii) the endocytic machinery localized mainly at the peri-active zone, and (iii) synaptic vesicles. Finally, we sketch scenarios, how presynaptic autophagic cargos are tagged and recruited and which cellular mechanisms may govern membrane-associated protein turnover in the presynapse.

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来源期刊
CiteScore
7.10
自引率
2.70%
发文量
74
审稿时长
14 weeks
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