Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to CCC (CCDC93, CCDC22, COMMD) and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α₅β₁ integrin. Through quantitative proteomic analysis, we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, that require SNX17-retriever to maintain their surface levels. Our identification of retriever establishes a major endosomal retrieval and recycling pathway.

中文翻译：

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Retriever 是一种多蛋白复合物，用于不依赖于逆转录酶的内体货物回收。

内吞作用进入内体网络后，整合膜蛋白会进行分类以进行溶酶体降解，或者被回收并循环回细胞表面。在这里，我们描述了一种古老且保守的多蛋白复合物的发现，该复合物协调货物回收和回收，重要的是，它在生化和功能上与已建立的逆转录酶途径不同。我们称这种复杂的“猎犬”；它是由 DSCR3、C16orf62 和 VPS29 组成的异源三聚体，与 retromer 具有惊人的相似性。我们确定寻回犬与货物适配器分选连接蛋白 17 (SNX17) 相关联，并与 CCC（CCDC93、CCDC22、COMMD）和 WASH 复合物结合，以防止溶酶体降解并促进 α 5 β 1 的_细胞表面_循环整合素。通过定量蛋白质组学分析，我们鉴定了 120 多种细胞表面蛋白，包括大量整合素、信号受体和溶质转运蛋白，它们需要 SNX17-retriever 来维持其表面水平。我们对寻回犬的鉴定建立了一个主要的内体检索和回收途径。