Komada Masayuki, Kitamura Naomi
Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B-16 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
J Biochem. 2005 Jan;137(1):1-8. doi: 10.1093/jb/mvi001.
Cell surface receptor proteins that have undergone endocytosis are transported to the endosome. From the endosome, ligand-activated receptor tyrosine kinases are further transported to the lysosome for degradation, a process called "receptor downregulation." By contrast, nutrient receptors, such as those for low-density lipoprotein and transferrin, are recycled back to the plasma membrane. Sorting of these two types of receptors occurs at the endosome, where ubiquitination of receptor proteins serves as the sorting signal. Namely, ubiquitinated receptors are incorporated into the lysosomal degradation pathway, whereas those that are not ubiquitinated are returned to the cell surface. Hrs and STAM are proteins that form a complex on the endosomal membrane. Recent studies have shown that the Hrs/STAM complex binds ubiquitin moieties and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.
经历过内吞作用的细胞表面受体蛋白会被转运至内体。在内体中，配体激活的受体酪氨酸激酶会被进一步转运至溶酶体进行降解，这一过程称为“受体下调”。相比之下，诸如低密度脂蛋白和转铁蛋白的营养受体则会被循环回质膜。这两种类型受体的分选发生在内体，在那里受体蛋白的泛素化作为分选信号。也就是说，泛素化的受体被纳入溶酶体降解途径，而未被泛素化的受体则返回细胞表面。Hrs和STAM是在内体膜上形成复合物的蛋白质。最近的研究表明，Hrs/STAM复合物结合泛素部分，并作为分选机制识别泛素化的受体，并将它们转移至进一步的连续溶酶体分选/运输过程。
