Graduate School of Pharmaceutical Sciences, Nagoya City University.
Exploratory Research Center on Life and Living Systems (ExCELLS).
Cell Struct Funct. 2024 Aug 27;49(2):47-55. doi: 10.1247/csf.24008. Epub 2024 Aug 22.
The Golgi apparatus, a crucial organelle involved in protein processing, including glycosylation, exhibits complex sub-structures, i.e., cis-, medial, and trans-cisternae. This study investigated the distribution of glycosyltransferases within the Golgi apparatus of mammalian cells via 3D super-resolution imaging. Focusing on human glycosyltransferases involved in N-glycan modification, we found that even enzymes presumed to coexist in the same Golgi compartment exhibit nuanced variations in localization. By artificially making their N-terminal regions [composed of a cytoplasmic, transmembrane, and stem segment (CTS)] identical, it was possible to enhance the degree of their colocalization, suggesting the decisive role of this region in determining the sub-Golgi localization of enzymes. Ultimately, this study reveals the molecular codes within CTS regions as key determinants of glycosyltransferase localization, providing insights into precise control over the positioning of glycosyltransferases, and consequently, the interactions between glycosyltransferases and substrate glycoproteins as cargoes in the secretory pathway. This study advances our understanding of Golgi organization and opens avenues for programming the glycosylation of proteins for clinical applications.Key words: Golgi apparatus, glycosyltransferase, 3D super-resolution imaging, N-glycosylation.
高尔基体是参与蛋白质加工的重要细胞器,包括糖基化,具有复杂的亚结构,即顺面、中间和反面腔。本研究通过三维超分辨率成像研究了糖基转移酶在哺乳动物细胞高尔基体中的分布。本研究聚焦于参与 N-糖链修饰的人类糖基转移酶,发现即使假定存在于同一高尔基体隔室中的酶也表现出细微的定位变化。通过人为地使它们的 N 端区域(由细胞质、跨膜和茎段(CTS)组成)相同,有可能增强它们的共定位程度,表明该区域在决定酶的亚高尔基体定位中起决定性作用。最终,本研究揭示了 CTS 区域内的分子密码作为糖基转移酶定位的关键决定因素,为精确控制糖基转移酶的定位以及糖基转移酶与作为分泌途径中货物的底物糖蛋白之间的相互作用提供了见解。本研究增进了我们对高尔基体组织的理解,并为临床应用中的蛋白质糖基化编程开辟了途径。
高尔基体;糖基转移酶;三维超分辨率成像;N-糖基化。