神经特异性O-GalNAc糖基转移酶在内质网中的功能机制研究

黏蛋白型O-GalNAc糖基化是一种重要的蛋白质翻译后修饰，已知与多种疾病的发生发展密切相关，对蛋白质的成熟加工，分泌功能定位、细胞间和细胞外基质的识别具有重要调控作用。然而蛋白质O-GalNAc糖基化在神经发育过程中的功能仍知之甚少。本研究以我们最早报道的神经特异性O-GalNAc糖基转移酶（ppGalNAc-T13)为研究对象，研究其在细胞内质网中的定位机制，运用化学生物学方法发现其相关O-GalNAc糖基化功能蛋白，结合神经发育中内质网流动现象，从糖基转移酶，糖蛋白，糖链三位一体的角度，在细胞和个体动物水平系统研究该酶在调控神经元内质网中O-GalNAc糖基化的分子机制，阐明其在神经元轴突或树突形成、糖蛋白分选和运输中的作用，为理解蛋白质O-GalNAc糖基化在神经系统疾病发生发展中的作用提供依据。

Mucin-type O-glycosylation (refer to protein O-GalNAc glycosylation) is an important post-translational modification. It is essential for protein maturation, secretion and localization, as well as for the interaction between cell and extracellular matrix. However, the function of O-GalNAc glycosylation in neural development is still little known. Previously, we have demonstrated an O-GalNAc glycosyltransferase (ppGalNAc-T13) is specifically expressed in the nervous system. This project is aimed to explore the mechanism of ppGalNAc-T13 in ER(endoplasmic reticulum), to screen and find the functional O-GalNAc substrates using chemical and biological method. Considering the phenomenon of the neuronal ER mobility, we will systematically study the molecular mechanism of ppGalNAc-T13 in the regulation of the O-GalNAc glycosylation occurs in the neuronal ER based on the cell models and individual animals (knockout mice). Our research could reveal the roles of ppGalNAc-T13 in axons or dendrites formation, glycoprotein sorting and trafficking, and finally provide new view for understanding the role of O-GalNAc glycosylation in the pathogenesis and progression of nervous system diseases.