期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 433, 期 1, 页码 90-95出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.02.059
关键词
Sortilin; Ubiquitination; ESCRTs; Lysosomal degradation; Intracellular trafficking; Palmitoylation
资金
- Canadian Institutes of Health Research (CIHR) [MOP-102754]
- Fonds de recherche du Quebec - Sante
- Alzheimer's Society of Canada
Sortilin is a transmembrane domain protein that has been implicated in the sorting of prosaposin and other soluble cargo from the Golgi to the lysosomal compartment. While the majority of the receptor is recycled back to the Golgi from endosomes, it is known that upon successive rounds of transport, a proportion of sortilin is degraded in lysosomes. Recently, it was shown that sortilin is palmitoylated and that this post-translational modification prevents its degradation and enables sortilin to efficiently traffic back to the Golgi. Thus palmitoylation can be used to modulate the amount of receptor and hence cargo reaching the lysosome. In this work, we demonstrate that non-palmitoylated sortilin is ubiquitinated and internalized into the lysosomal compartment via the ESCRT pathway for degradation. Furthermore, we identified Nedd4 as an E3 ubiquitin ligase that mediates this post-translational modification. We propose a model where palmitoylation and ubiquitination play opposite roles in the stability and turnover of sortilin and serve as a control mechanism that balances the amount of lysosomal sorting and trafficking in cells. (c) 2013 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据