高尔基体 pH 平衡通过膜蛋白的 N-糖基化稳定溶酶体膜。

IF 3.3 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2024-07-30 Print Date: 2024-10-01 DOI:10.26508/lsa.202402677
Yu-Shin Sou, Junji Yamaguchi, Keisuke Masuda, Yasuo Uchiyama, Yusuke Maeda, Masato Koike
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引用次数: 0

摘要

蛋白质糖基化在各种细胞功能中发挥着至关重要的作用,其中许多功能都发生在高尔基体内。高尔基体 pH 调节器(GPHR)对高尔基体的正常运作至关重要。溶酶体膜含有大量高度糖基化的膜蛋白。本研究使用 Gphr 缺失的 MEFs 研究了高尔基体腔 pH 在溶酶体膜蛋白 N-糖基化中的作用以及这种蛋白修饰对膜稳定性的影响。我们发现 Gphr 缺乏会导致高尔基体腔 pH 失衡,从而导致蛋白质 N-糖基化异常,表现为糖基化聚糖的减少和糖蛋白分子量的明显降低。使用 FRAP 和 PLA 进行的进一步实验显示,Gphr 缺乏会阻碍高尔基体内糖基转移酶的转运动态和接近条件。此外,溶酶体膜蛋白的不完全N-糖基化也影响了溶酶体膜的稳定性,溶酶体损伤的易感性增加就证明了这一点。因此,本研究强调了高尔基体 pH 值调节在控制蛋白质糖基化中的关键作用,以及高尔基体功能障碍对溶酶体膜稳定性的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Golgi pH homeostasis stabilizes the lysosomal membrane through N-glycosylation of membrane proteins.

Protein glycosylation plays a vital role in various cellular functions, many of which occur within the Golgi apparatus. The Golgi pH regulator (GPHR) is essential for the proper functioning of the Golgi apparatus. The lysosomal membrane contains highly glycosylated membrane proteins in abundance. This study investigated the role of the Golgi luminal pH in N-glycosylation of lysosomal membrane proteins and the effect of this protein modification on membrane stability using Gphr-deficient MEFs. We showed that Gphr deficiency causes an imbalance in the Golgi luminal pH, resulting in abnormal protein N-glycosylation, indicated by a reduction in sialylated glycans and markedly reduced molecular weight of glycoproteins. Further experiments using FRAP and PLA revealed that Gphr deficiency prevented the trafficking dynamics and proximity condition of glycosyltransferases in the Golgi apparatus. In addition, incomplete N-glycosylation of lysosomal membrane proteins affected lysosomal membrane stability, as demonstrated by the increased susceptibility to lysosomal damage. Thus, this study highlights the critical role of Golgi pH regulation in controlling protein glycosylation and the impact of Golgi dysfunction on lysosomal membrane stability.

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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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