PRICKLE3保护VANGL蛋白免受CK1介导的酸化和RNF43介导的降解.
Katarzyna A Radaszkiewicz1, Tomasz W Radaszkiewicz1, Pavla Kolářová1
1Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia.
Communications biology
|December 27, 2025
概括
PRICKLE3是WNT/平面细胞极性 (PCP) 信号的关键调节器. 它通过防止酸化来稳定VANGL1/2蛋白质,这对于细胞极性和组织发育至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- WNT/平面细胞极性 (PCP) 途径对脊椎动物发育至关重要,控制细胞极性和组织组织.
- 在WNT/PCP途径中,个别的PRICKLE蛋白功能尚未完全阐明.
- 了解PRICKLE蛋白机制对于理解发育过程和疾病至关重要.
研究的目的:
- 确定和描述PRICKLE3在WNT/PCP信号传输中的作用.
- 阐明PRICKLE3调节WNT/PCP组件的分子机制.
- 为研究PRICKLE蛋白家族提供新的分子工具.
主要方法:
- 增强的近距离生物化 (miniTurboID) 与质谱相结合,以确定蛋白质相互作用.
- 免疫洗和实时成像,以评估蛋白质的稳定性和定位.
- 在人类细胞,Xenopus laevis和斑马鱼 (Danio rerio) 胚胎中进行功能性测试.
主要成果:
- 确定了PRICKLE3作为跨物种WNT/PCP信号传递的中央调节器.
- 在血膜上,PRICKLE3与VANGL1和VANGL2结合.
- PRICKLE3通过抑制氨酸激酶1ε (CK1ε) 介导的酸化和调节RNF43活性来选择性地稳定VANGL1/2.
- 而PRICKLE1对VANGL蛋白没有表现出类似的稳定作用.
结论:
- PRICKLE3采用一种独特的机制,通过抑制CK1ε和抑制RNF43.3来稳定VANGL复合体.
- 这种PRICKLE3特异性功能对于WNT/PCP通路调节至关重要,影响细胞极性和组织结构.
- 这项研究提供了详细的互动组和有价值的工具,用于未来的研究在发育和疾病中皮蛋白.
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