OGT调节中心体组装及功能的分子机制

O-GlcNAc修饰是细胞内蛋白的一种重要的翻译后修饰，参与调控多种生命进程；O-GlcNAc修饰失调导致多种疾病，如糖尿病、肿瘤、神经退行性疾病等。在前期的工作中，我们发现调控O-GlcNAc修饰的酶OGT定位于中心体，并参与纤毛发生；然而，OGT对中心体组装及功能的影响尚不清楚。在本研究中，我们将从OGT在中心体处的特殊定位出发，探究OGT对中心体的直接影响；通过超高分辨显微技术，检测O-GlcNAc修饰是否参与调控中心体的组装，并进一步影响中心体相关的功能；同时通过质谱鉴定出具有O-GlcNAc修饰的中心体相关蛋白，揭示OGT调节中心体结构及功能的下游机制。本研究将阐释OGT在中心体处的作用，可以进一步丰富O-GlcNAc修饰在细胞中的功能，为相关疾病治疗提供理论依据。

O-GlcNAcylation is an important post-translational modification that participates in many biological processes. Dysregulation of O-GlcNAcylation leads to a wide range of human diseases, including diabetes, tumor, and neurodegeneration. We have previously found that OGT, the enzyme catalyzing O-GlcNAcylation, localized to centrosomes and participated in ciliogenesis. However, the precise mechanism of how OGT regulates the assembly and function of centrosomes remains elusive. In this study, we aim to investigate the molecular regulation of OGT on centrosomes. Utilizing three-dimensional structured illumination microscopy (3D-SIM), we will find out whether O-GlcNAcylation participates in regulating the assembly of centrosomes and the functions of centrosomes. We will also try to identify O-GlcNAcylated proteins as substrates of OGT related to centrosomes by mass spectrometry and reveal the underlying mechanism of OGT in regulating the structure and function of centrosomes. This study will offer molecular insight of OGT at the centrosomes, thus holding promise for the possible treatment of related diseases.