Sorting Nexins and Intracellular Protein Trafficking

分类连接蛋白（SNXs）是一个哺乳动物蛋白家族，包含新描述的结构域，称为PX结构域。许多snx也与酵母中正常蛋白质运输所需的几种蛋白质具有密切的同源性。SNX1和SNX2是vp5p的同源基因，vp5p是一种参与蛋白质从晚期核内体向TGN逆行运输的蛋白质。SNX3是Grd19p的同源物，Grd19p是一种在高尔基体中保留Kex2p等蛋白质所需的蛋白质。SNX8是Mvp1p的近亲，Mvp1p是一种与动力蛋白样蛋白相互作用的蛋白质。我们已经获得了含有Vps5p的多聚复合体的其他几个组分（即Vps26， Vps35和Vps29）的人类同源物的cdna。我们已经使用酵母两种杂交分析来表征许多这些蛋白质之间的相互作用。我们的数据与人类Vps35通过提供SNX1、hVps26和hVps36的结合位点作为多聚物复合物核心的模型一致。此外，我们已经证明了一些snx与各种受体酪氨酸激酶（例如EGF， PDGF和胰岛素受体），瘦素受体的长形式和各种丝氨酸/苏氨酸激酶（例如tgf β和激活素受体）相互作用。最近的功能研究表明，SNX15通过内吞途径在转运中起着至关重要的作用。进一步的研究正在进行中，以阐明其他分选连接蛋白及其相关蛋白在哺乳动物细胞内蛋白质运输中的作用。

Sorting nexins (SNXs)are a family of mammalian proteins that contain newly described domain termed the PX domain. Numerous SNXs also have close homology to several proteins that are required for normal protein trafficking in yeast. SNX1 and SNX2 are orthologs of Vps5p, a protein involved in retrograde traffic of proteins from late endosomes to the TGN. SNX3 is the ortholog of Grd19p, a protein required to retain proteins such as Kex2p in the Golgi. SNX8 is a close homolog of Mvp1p, a protein that interacts with a dynamin-like protein. We have obtained cDNAs for human homologs of several other components of the multimeric complex containing Vps5p (i.e., Vps26, Vps35 and Vps29. We have used yeast two hybrid assays to characterize the interactions among many of these proteins. Our data are consistent with a model in which human Vps35 serves as the core of a multimeric complex by providing binding sites for SNX1,hVps26 and hVps36. In addition, we have demonstrated that several of the SNXs interact with various receptor tyrosine kinases (e.g. receptors for EGF, PDGF and insulin), the long form of the leptin receptors, and various serine/threonine kinases (e.g. receptors for TGFbeta and activin). Recent functional studies have demonstrated that SNX15 plays a crucial role in trafficking through the endocytic pathway. Further studies are underway to elucidate the roles of the other sorting nexins and their associated proteins in intracellular protein trafficking in mammalian cells.