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RIP at the Synapse and the Role of Intracellular Domains in Neurons
Archives of Computational Methods in Engineering ( IF 9.7 ) Pub Date : 2019-07-25 , DOI: 10.1007/s12017-019-08556-4
Yan Jun Lee , Toh Hean Ch’ng

Abstract

Regulated intramembrane proteolysis (RIP) occurs in a cell when transmembrane proteins are cleaved by intramembrane proteases such as secretases to generate soluble protein fragments in the extracellular environment and the cytosol. In the cytosol, these soluble intracellular domains (ICDs) have local functions near the site of cleavage or in many cases, translocate to the nucleus to modulate gene expression. While the mechanism of RIP is relatively well studied, the fate and function of ICDs for most substrate proteins remain poorly characterized. In neurons, RIP occurs in various subcellular compartments including at the synapse. In this review, we summarize current research on RIP in neurons, focusing specifically on synaptic proteins where the presence and function of the ICDs have been reported. We also briefly discuss activity-driven processing of RIP substrates at the synapse and the cellular machinery that support long-distance transport of ICDs from the synapse to the nucleus. Finally, we describe future challenges in this field of research in the context of understanding the contribution of ICDs in neuronal function.



中文翻译:

RIP在突触和神经元细胞内域的作用。

摘要

当跨膜蛋白被诸如分泌酶之类的膜内蛋白酶切割以在细胞外环境和细胞质中产生可溶性蛋白片段时,调节的膜内蛋白水解(RIP)发生在细胞中。在胞质溶胶中,这些可溶性细胞内结构域(ICD)在切割位点附近具有局部功能,或者在许多情况下,易位至细胞核以调节基因表达。尽管对RIP的机制进行了比较充分的研究,但ICD对大多数底物蛋白的结局和功能仍知之甚少。在神经元中,RIP发生在包括突触在内的各种亚细胞区室中。在这篇综述中,我们总结了神经元RIP的最新研究,特别是针对已报道了ICD的存在和功能的突触蛋白。我们还简要讨论了在突触和支持ICD从突触到核的长距离运输的细胞机械的RIP底物的活动驱动的处理。最后,我们在理解ICD在神经元功能中的作用的背景下描述了该研究领域的未来挑战。

更新日期:2020-03-26
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