We identify BEACH domain-containing proteins (BDCPs) as novel membrane coat proteins involved in the sorting of transmembrane proteins (TMPs) on the trans-Golgi network and tubular sorting endosomes. The seven typical mammalian BDCPs share a predicted alpha-solenoid-beta propeller structure, suggesting they have a protocoatomer origin and function. We map the subcellular localization of seven BDCPs based on their dynamic colocalization with RAB and ARF small GTPases and identify five typical BDCPs on subdomains of dynamic tubular-vesicular compartments on the intersection of endocytic recycling and post-Golgi secretory pathways. We demonstrate that BDCPs interact directly with the cytosolic tails of selected TMPs and identify a subset of TMPs, whose trafficking to the plasma membrane is affected in cells lacking BDCP. We propose that the competitive binding of BDCPs and clathrin coat adaptors to the cytosolic tails of TMPs, followed by their clustering to distinct subdomains of secretory/recycling tubules function as a mechanism for sorting of TMPs in pleomorphic tubular-vesicular compartments that lack a clathrin coat.

中文翻译：

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BEACH 结构域蛋白在分泌和内吞途径中起货物分选接头蛋白的作用。


我们将 BEACH 结构域蛋白 （BDCPs） 鉴定为新型膜外壳蛋白，参与反式高尔基体网络上跨膜蛋白 （TMP） 的分选和肾小管分选内体。七种典型的哺乳动物 BDCP 共享预测的 α-螺线管-β 螺旋桨结构，表明它们具有原壳体起源和功能。我们根据 7 个 BDCP 与 RAB 和 ARF 小 GTP 酶的动态共定位绘制了它们的亚细胞定位图谱，并在内吞循环和高尔基体后分泌途径交叉点的动态肾小管-囊泡区室的亚结构域上鉴定了 5 个典型的 BDCP。我们证明 BDCP 直接与选定 TMP 的胞质尾部相互作用，并鉴定了 TMP 的一个子集，其向质膜的运输在缺乏 BDCP 的细胞中受到影响。我们提出，BDCP 和网格蛋白外壳接头与 TMP 胞质尾部的竞争性结合，然后它们聚集到分泌/回收小管的不同亚结构域，作为在缺乏网格蛋白涂层的多形性管状囊泡区中对 TMP 进行分类的机制。