Sorting Nexins and Intracellular Protein Trafficking

分类连接蛋白是一类含有Px结构域的哺乳动物蛋白质家族，这些蛋白质与酵母中正常的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Vps5p的紧密同源物，Vps5p是一种参与蛋白质从晚期内体逆行运输到高尔基体的蛋白质。SNX3是Grd19p的同源基因，Grd19p是一种在高尔基体中保留Kex2p等蛋白质所必需的蛋白质。SNX8是Mvp1p的近亲同系物，Mvp1p是一种与动力蛋白样蛋白(Vps1p)相互作用的蛋白质。我们已经获得了几个排序连接素(SNX1-4、8和15)的cDNA，也获得了含有Vps5p的多聚体复合体的其他几个组分(即Vps26p、Vps29p和Vps35p)的人类同源物的cDNA。我们已经证明，这些蛋白中的几个与各种受体酪氨酸激酶(例如，胰岛素、EGF和PDGF的受体)以及瘦素受体的长亚型相互作用。此外，我们还使用酵母双杂交系统来表征这些蛋白质之间的相互作用。这些数据与人类VPS35通过提供SNX1、hVps26和hVps29的结合位点作为多聚体复合体的核心的模型是一致的。目前正在进行研究，以阐明这些蛋白质在哺乳动物细胞内蛋白质运输中的作用。-蛋白运输、空泡蛋白分选、内体、溶酶体、高尔基体、胰岛素、瘦素、受体酪氨酸激酶

Sorting nexins are a family of mammalian proteins that contain PX domains with close homology to several proteins that are required for normal protein trafficking in yeast. SNX1 and SNX2 are close homologs of Vps5p, a protein involved in retrograde traffic of proteins from late endosomes to the Golgi. 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 (Vps1p). We have obtained cDNAs for several sorting nexins (SNX1-4, 8, and 15), and also obtained cDNAs for human homologs of several other components of the multimeric complex containing Vps5p (i.e., Vps26p, Vps29p, and Vps35p). We have demonstrated that several of these proteins interact with various receptor tyrosine kinases (e.g., receptors for insulin, EGF, and PDGF) and also with the long isoform of the leptin receptor. In addition, we have used the yeast two hybrid system to characterize the interactions among these proteins. The 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 hVps29. Studies are underway to elucidate the roles of these proteins in protein trafficking within mammalian cells. - protein trafficking, vacuolar protein sorting, endosome, lysosome, golgi, insulin, leptin, receptor tyrosine kinase