The iTRAPs: Guardians of Synaptic Vesicle Cargo Retrieval During Endocytosis.

The iTRAPs: Guardians of Synaptic Vesicle Cargo Retrieval During Endocytosis.
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DOI:
10.3389/fnsyn.2016.00001
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发表时间:
2016
影响因子:
3.7
通讯作者:
Cousin MA
Cousin MA
中科院分区:
医学3区
文献类型:
--
作者:
Gordon SL;Cousin MA

文献摘要

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内吞过程中突触囊泡的重新形成对维持中枢神经末梢的神经传递是必不可少的。新形成的SV必须以正确的化学计量产生正确的蛋白质货物,才能发挥胞吐作用。经典的网格蛋白衔接蛋白复合物在这方面的分类和聚集突触囊泡货物中发挥关键作用。然而,越来越明显的是,存在额外的“自动防故障”机制,以确保准确检索必要的货物分子。例如,单体衔接蛋白AP 180/CALM和stonin-2分别是有效检索小突触泡蛋白II(sybII)和突触结合蛋白-1所需的。此外,最近的研究表明,sybII和synaptotagmin-1与其他SV货物相互作用,以确保高保真的检索。这些货物是突触素(sybII)和SV 2A(突触结合蛋白-1)。在这篇综述中,我们总结了目前的知识有关的检索机制sybII和synaptotagmin-1在胞吞作用。我们还定义了一个新的功能组SV分子,促进检索他们的相互作用的合作伙伴,并设置标准。我们将这些分子称为内在贩运伙伴(iTRAPs),我们讨论了这组功能如何影响健康和疾病的突触前表现。
The reformation of synaptic vesicles (SVs) during endocytosis is essential for the maintenance of neurotransmission in central nerve terminals. Newly formed SVs must be generated with the correct protein cargo in the correct stoichiometry to be functional for exocytosis. Classical clathrin adaptor protein complexes play a key role in sorting and clustering synaptic vesicle cargo in this regard. However it is becoming increasingly apparent that additional “fail-safe” mechanisms exist to ensure the accurate retrieval of essential cargo molecules. For example, the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval. These cargoes are synaptophysin (for sybII) and SV2A (for synaptotagmin-1). In this review, we summarize current knowledge regarding the retrieval mechanisms for both sybII and synaptotagmin-1 during endocytosis. We also define and set criteria for a new functional group of SV molecules that facilitate the retrieval of their interaction partners. We have termed these molecules intrinsic trafficking partners (iTRAPs) and we discuss how the function of this group impacts on presynaptic performance in both health and disease.