Sorting Nexins and Intracellular Protein Trafficking

分选连接蛋白（SNXs）是哺乳动物蛋白家族中的一个成员，其结构域被称为PX结构域。 许多SNX还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。 SNX 1和SNX 2是Vps 5 p的直系同源物，Vps 5 p是一种参与蛋白质从晚期内体到TGN的逆行运输的蛋白质。 SNX 3是Grd 19 p的直系同源物，Grd 19 p是一种将Kex 2 p等蛋白质保留在高尔基体中所需的蛋白质。 SNX 8是Mvp 1 p的同源物，Mvp 1 p是一种与发动蛋白样蛋白相互作用的蛋白质。 我们已经获得了含有Vps 5 p的多聚体复合物的几种其他组分的人同源物的cDNA（即，Vps 26、Vps 35和Vps 29。 我们已经使用酵母双杂交检测来表征这些蛋白质之间的相互作用。 我们的数据是一致的模型，其中人Vps 35作为一个多聚体复合物的核心，通过提供SNX 1，hVps 26和hVps 36的结合位点。此外，我们已经证明了几种SNX与各种受体酪氨酸激酶（例如EGF、PDGF和胰岛素的受体）、长型瘦素受体和各种丝氨酸/苏氨酸激酶（例如TGF β和激活素的受体）相互作用。 最近的功能研究表明，SNX 15通过内吞途径在运输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.