ppGalNAc-T18调控细胞O-糖基化蛋白质成熟分泌过程的作用机制研究

蛋白质糖基化影响蛋白质的生物功能。在蛋白质成熟和分泌过程中，底物蛋白和糖基转移酶的正确折叠及其正确的亚细胞定位是蛋白质糖基化的前题条件，对维持细胞亚细胞器结构稳态具有重要意义。黏蛋白型O-GalNAc糖基化发生在高尔基体中，但是O-糖基化蛋白进入高尔基体之前的蛋白折叠和分拣机制并不清楚。2019年我们发现报道了内质网定位的糖基转移酶ppGalNAc-T18以非酶促反应作用维持内质网稳态并调控细胞整体O-糖基化。本项目在分析T18基因敲除小鼠肺组织蛋白质组学数据的基础上，研究 1）内质网和ERGIC中T18调控黏蛋白成熟分泌的机制，2）T18通过COPI小泡对Agr2和其他糖基转移酶表达和定位的作用机制，阐明T18在糖基化底物折叠和分泌，以及蛋白膜泡运输中糖基转移酶的表达和定位中的分子机制，为全面理解蛋白质O-GalNAc糖基化的调控机制提供新依据。

Glycosylation affects the biological functions of proteins. The exact folding and localization of substrates and glycosyltransferases are necessary for protein glycosylation and important to maintain organelle homeostasis. Mucin-type O-GalNAc glycosylation initiates at Golgi. However it is rarely known about the folding and sorting mechanisms of protein. We have reported the ER-localized glycotransferase ppGalNAc-T18 could regulate the O-glycosylation and ER homeostasis in a non-catalytic manner in 2019. Based on the proteomics data of ppGalNAc-T18 knockout mice, this project aims to study the roles of ppGalNAc-T18 in regulating the processing and secreting of mucins in ER and ERGIC. Besides, we attempt to elucidate the molecular mechanism of ppGalNAc-T18 in regulating the localization of Agr2 and other glycosyltransferases, with the hope to provide important insights into the understanding of O-GalNAc glycosylation.