The retromer complex - endosomal protein recycling and beyond
The retromer complex - endosomal protein recycling and beyond
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DOI：
10.1242/jcs.103440
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发表时间：
2012-10-15
影响因子：
4
通讯作者：
Seaman, Matthew N. J.
中科院分区：
文献类型：
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作者：
Seaman, Matthew N. J.
逆转录复合体是内体蛋白分选机制的重要组成部分，在所有真核生物中都是保守的。逆转录酶与内体到高尔基体的获取途径密切相关，是维持反式高尔基网络中水解酶受体活性的必要条件。最近对逆转录酶的研究进展已经发现了新的逆转录酶相互作用蛋白，包括WASH复合物和货物如Wntless/MIG-14蛋白，这些蛋白现在将逆转录酶的作用扩展到核内体到高尔基体的途径之外，并揭示了逆转录酶在核内体到质膜的分类和信号事件的调节方面是必需的。反转录复合体和其他大分子蛋白质复合体之间的相互作用现在显示了内体蛋白质分选是如何与肌动蛋白组装和沿微管移动协调的，并将反转录复合体置于控制内体蛋白质分选的复杂蛋白质机制的中心。逆转录酶介导的内体蛋白分选失调导致各种病理，包括神经退行性疾病，如阿尔茨海默病和痉挛性截瘫，这些病理的机制开始被理解。在这篇评论中，我将重点介绍逆转录酶介导的内体蛋白分选的最新进展，并讨论逆转录酶如何促进一系列不同的生理过程。
The retromer complex is a vital element of the endosomal protein sorting machinery that is conserved across all eukaryotes. Retromer is most closely associated with the endosome-to-Golgi retrieval pathway and is necessary to maintain an active pool of hydrolase receptors in the trans-Golgi network. Recent progress in studies of retromer have identified new retromer-interacting proteins, including the WASH complex and cargo such as the Wntless/MIG-14 protein, which now extends the role of retromer beyond the endosome-to-Golgi pathway and has revealed that retromer is required for aspects of endosome-to-plasma membrane sorting and regulation of signalling events. The interactions between the retromer complex and other macromolecular protein complexes now show how endosomal protein sorting is coordinated with actin assembly and movement along microtubules, and place retromer squarely at the centre of a complex set of protein machinery that governs endosomal protein sorting. Dysregulation of retromer-mediated endosomal protein sorting leads to various pathologies, including neurodegenerative diseases such as Alzheimer disease and spastic paraplegia and the mechanisms underlying these pathologies are starting to be understood. In this Commentary, I will highlight recent advances in the understanding of retromer-mediated endosomal protein sorting and discuss how retromer contributes to a diverse set of physiological processes.