The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein
The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein
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DOI：
10.1093/emboj/20.9.2180
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发表时间：
2001-05-01
期刊：
影响因子：
11.4
通讯作者：
Petersen, CM
中科院分区：
文献类型：
--
作者：
Nielsen, MS;Madsen, P;Petersen, CM
山梨素属于一个正在成长的多配基1型受体家族，与酵母受体Vps10p同源。根据结构特征和山梨素在细胞内的优势，我们认为它既是合成途径中配体的分选受体，也是细胞膜上的分选受体。为了验证这一假设，我们在这里研究了含有山梨素尾巴结构的嵌合受体的细胞运输。我们报告说，符合YXX Phi和二亮氨酸基序的分选信号介导了山梨素嵌合体的快速内吞，这些嵌合体随后进入反式高尔基体网络，显示很少或没有回收。此外，我们还发现，在甘露糖6-磷酸受体敲除细胞中表达的阳离子非依赖的甘露糖6-磷酸受体(MPR300)-山梨素嵌合体几乎和MPR300本身一样有效地将新合成的β-己糖氨酸酶和β-葡萄糖醛酸苷酶运输到溶酶体，并证实山梨素尾部含有有效的高尔基内体分选信号。最后，我们提供的证据表明，山梨素是第一个哺乳动物受体的例子，以最近描述的胞浆分选蛋白GGA家族为靶标，该家族为Vps10p介导的酵母羧基肽酶Y分选提供了条件。
Sortilin belongs to a growing family of multiligand type-1 receptors with homology to the yeast receptor Vps10p. Based on structural features and sortilin's intracellular predominance, we have proposed it to be a sorting receptor for ligands in the synthetic pathway as well as on the cell membrane. To test this hypothesis we examine here the cellular trafficking of chimeric receptors containing constructs of the sortilin tail. We report that sorting signals conforming to YXX Phi, and dileucine motifs mediate rapid endocytosis of sortilin chimeras, which subsequently travel to the trans-Golgi network, showing little or no recycling. Furthermore, we found that cation-independent mannose 6-phosphate receptor (MPR300)-sortilin chimeras, expressed in mannose 6-phosphate receptor knockout cells, were almost as efficient as MPR300 itself for transport of newly synthesized beta -hexosaminidase and beta -glucuronidase to lysosomes, and established that the sortilin tail contains potent signals for Golgi-endosome sorting. Finally, we provide evidence suggesting that sortilin is the first example of a mammalian receptor targeted by the recently described GGA family of cytosolic sorting proteins, which condition the Vps10p-mediated sorting of yeast carboxypeptidase Y.