氨酸类型O-甘氨酸调节蛋白质甘氨酸的稳定性和冠状细胞的成熟
Xiaolin Dong1,2, Sydney Bedillion1,2, Kaleigh E Gosnell2
1Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.
bioRxiv : the preprint server for biology
|December 19, 2025
概括
扩展的O-甘氨酸和肝素硫酸蛋白甘氨酸 (HSPGs) 在功能上相互作用. 丢失的O-甘氨酸会损害蛋白质甘氨酸的稳定性和基生成,揭示了新的糖化在发育和疾病中的作用.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 发育生物学 发展生物学
背景情况:
- 糖化是一种重要的翻译后修饰,影响蛋白质功能和组织发育.
- 不同的O-甘氨酸子类在协调组织发育中的确切作用尚未完全理解.
- 肝酸硫酸蛋白质甘 (HSPGs) 是细胞信号和组织组织的关键调节剂.
研究的目的:
- 为了研究扩展的素类型O-甘氨酸和HSPG之间的功能交叉.
- 阐明O-甘氨酸缺乏对细胞信号和细胞外矩阵重塑的影响.
- 了解O-甘氨酸在基生成中的作用及其对甘氨基化乱的贡献.
主要方法:
- 在人体冠状细胞中,C1GALT1和COSMC的遗传移除.
- 对细胞表面HSPG水平和纤维细胞生长因子 (FGF) 结合的分析.
- 转录组和秘密组分析.
- 评估Syndecan-1和CD44v3的表达和功能.
- 在增长板状的chondroprogenitors中评估chondrogenesis.
主要成果:
- 在O-糖化 (C1GALT1或COSMC) 的遗传缺陷减少了细胞表面的HSPG和FGF结合.
- 在缺陷细胞中观察到MAPK/ERK信号受损和受损的原生.
- 切断O-GalNAc甘氨酸导致Syndecan-1水平降低,并降低了CD44v3介导的FGF1结合.
- 细胞外矩阵重塑和选择性蛋白质甘氨酸表达损失发生在缺陷细胞中.
结论:
- 扩展的木类型O-甘氨酸对于维持蛋白质甘氨酸的稳定性和功能至关重要.
- O-甘氨酸和HSPG之间的功能交叉是正常原生成的必要条件.
- 这些发现突出了对发育至关重要的跨调节性甘化机制,并与与甘化相关的疾病相关.
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