期刊
EMBO JOURNAL
卷 40, 期 20, 页码 -出版社
WILEY
DOI: 10.15252/embj.2021107766
关键词
glucosylceramide synthase; glycosphingolipids; glycosylation; Golgi apparatus; GRASP55
资金
- Italian Cystic Fibrosis Research Foundation [6-2019]
- POR Campania project
- Fondazione Italiana per la Ricerca sul Cancro (FIRC Fellowship ) [15111]
- AIRC [IG 15767, IG 20786]
- TERABIO
- PON-IMPARA
- S.A.T.I.N
- G.D.A
- EPFL institutional fund
- Kristian Gerhard Jebsen Foundation
- Swiss National Science Foundation (SNSF) [310030_184926]
- Swiss National Science Foundation (SNF) [310030_184926] Funding Source: Swiss National Science Foundation (SNF)
The Golgi matrix protein GRASP55 plays a crucial role in regulating the compartmentalized localization of key enzymes involved in glycosphingolipid biosynthesis. Lack of GRASP55 or expression of mutant enzymes without GRASP55 binding sites can affect the synthesis of glycosphingolipids by altering metabolic flux.
The Golgi apparatus, the main glycosylation station of the cell, consists of a stack of discontinuous cisternae. Glycosylation enzymes are usually concentrated in one or two specific cisternae along the cis-trans axis of the organelle. How such compartmentalized localization of enzymes is achieved and how it contributes to glycosylation are not clear. Here, we show that the Golgi matrix protein GRASP55 directs the compartmentalized localization of key enzymes involved in glycosphingolipid (GSL) biosynthesis. GRASP55 binds to these enzymes and prevents their entry into COPI-based retrograde transport vesicles, thus concentrating them in the trans-Golgi. In genome-edited cells lacking GRASP55, or in cells expressing mutant enzymes without GRASP55 binding sites, these enzymes relocate to the cis-Golgi, which affects glycosphingolipid biosynthesis by changing flux across metabolic branch points. These findings reveal a mechanism by which a matrix protein regulates polarized localization of glycosylation enzymes in the Golgi and controls competition in glycan biosynthesis.
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