Program in Cell Biology, The Hospital for Sick Children and Biochemistry Department, University of Toronto, Toronto, Canada.
Pflugers Arch. 2011 Jan;461(1):1-21. doi: 10.1007/s00424-010-0893-2. Epub 2010 Oct 23.
Ion channels and transporters play a critical role in ion and fluid homeostasis and thus in normal animal physiology and pathology. Tight regulation of these transmembrane proteins is therefore essential. In recent years, many studies have focused their attention on the role of the ubiquitin system in regulating ion channels and transporters, initialed by the discoveries of the role of this system in processing of Cystic Fibrosis Transmembrane Regulator (CFTR), and in regulating endocytosis of the epithelial Na(+) channel (ENaC) by the Nedd4 family of ubiquitin ligases (mainly Nedd4-2). In this review, we discuss the role of the ubiquitin system in ER Associated Degradation (ERAD) of ion channels, and in the regulation of endocytosis and lysosomal sorting of ion channels and transporters, focusing primarily in mammalian cells. We also briefly discuss the role of ubiquitin like molecules (such as SUMO) in such regulation, for which much less is known so far.
离子通道和转运体在离子和液体稳态中起着关键作用，因此在正常动物生理学和病理学中也是如此。因此，这些跨膜蛋白的严格调控是必不可少的。近年来，许多研究都集中在泛素系统在调节离子通道和转运体中的作用上，这一系统在囊性纤维化跨膜转导调节因子（CFTR）的加工以及Nedd4 家族泛素连接酶（主要是 Nedd4-2）对上皮钠通道（ENaC）的内吞作用中的作用的发现，最初引起了人们的关注。在这篇综述中，我们讨论了泛素系统在离子通道的内质网相关降解（ERAD）以及离子通道和转运体的内吞作用和溶酶体分选中的作用，主要集中在哺乳动物细胞上。我们还简要讨论了泛素样分子（如 SUMO）在这种调节中的作用，目前对此知之甚少。
