与将N-糖基化视为常规维护功能的普遍看法相反，研究人员发现了一条调节OST-A活性的内质网（ER）通路。遗传分析将OST-A与HSP90B1（一种膜受体的ER伴侣蛋白）和CCDC134（一种ER腔内蛋白）联系起来。
在HSP90B1转运到ER的过程中，其N端肽段引导了包含CCDC134和OST-A的易位复合体的组装，该复合体在折叠期间保护HSP90B1，防止其过度糖基化和降解。该通路的破坏会损害WNT和IGF1R信号传导，并导致骨发育障碍——成骨不全症。
因此，N-糖基化可以通过ER中的特异性因子进行调控，从而控制细胞表面受体信号传导和组织发育。
据介绍，人体五分之一的蛋白质在ER中通过两种寡糖基转移酶OST-A和OST-B进行N-糖基化。
附：英文原文
Title: Regulated N-glycosylation controls chaperone function and receptor trafficking
Author: Mengxiao Ma, Ramin Dubey, Annie Jen, Ganesh V. Pusapati, Bharti Singal, Evgenia Shishkova, Katherine A. Overmyer, Valérie Cormier-Daire, Juliette Fedry, L. Aravind, Joshua J. Coon, Rajat Rohatgi
Issue&Volume: 2024-11-08
Abstract: One-fifth of human proteins are N-glycosylated in the endoplasmic reticulum (ER) by two oligosaccharyltransferases, OST-A and OST-B. Contrary to the prevailing view of N-glycosylation as a housekeeping function, we identified an ER pathway that modulates the activity of OST-A. Genetic analyses linked OST-A to HSP90B1, an ER chaperone for membrane receptors, and CCDC134, an ER luminal protein. During its translocation into the ER, an N-terminal peptide in HSP90B1 templates the assembly of a translocon complex containing CCDC134 and OST-A that protects HSP90B1 during folding, preventing its hyperglycosylation and degradation. Disruption of this pathway impairs WNT and IGF1R signaling and causes the bone developmental disorder osteogenesis imperfecta. Thus, N-glycosylation can be regulated by specificity factors in the ER to control cell surface receptor signaling and tissue development.
DOI: adp7201
Source: https://www.science.org/doi/10.1126/science.adp7201