Katzmann D J, Babst M, Emr S D
Division of Cellular and Molecular Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Cell. 2001 Jul 27;106(2):145-55. doi: 10.1016/s0092-8674(01)00434-2.
The multivesicular body (MVB) pathway is responsible for both the biosynthetic delivery of lysosomal hydrolases and the downregulation of numerous activated cell surface receptors which are degraded in the lysosome. We demonstrate that ubiquitination serves as a signal for sorting into the MVB pathway. In addition, we characterize a 350 kDa complex, ESCRT-I (composed of Vps23, Vps28, and Vps37), that recognizes ubiquitinated MVB cargo and whose function is required for sorting into MVB vesicles. This recognition event depends on a conserved UBC-like domain in Vps23. We propose that ESCRT-I represents a conserved component of the endosomal sorting machinery that functions in both yeast and mammalian cells to couple ubiquitin modification to protein sorting and receptor downregulation in the MVB pathway.
多囊泡体（MVB）途径既负责溶酶体水解酶的生物合成运输，也负责众多在溶酶体中降解的活化细胞表面受体的下调。我们证明泛素化作为一种分选进入MVB途径的信号。此外，我们鉴定了一种350 kDa的复合物，ESCRT-I（由Vps23、Vps28和Vps37组成），它识别泛素化的MVB货物，并且其功能是分选进入MVB囊泡所必需的。这种识别事件依赖于Vps23中一个保守的类UBC结构域。我们提出ESCRT-I代表内体分选机制的一个保守组分，其在酵母和哺乳动物细胞中均发挥作用，将泛素修饰与MVB途径中的蛋白质分选和受体下调相偶联。
