一个基于ubiquitin的效应剂-抑制剂开关协调早期的大脑,面和皮肤发育
Anthony J Asmar1, Shaun R Abrams1,2, Jenny Hsin2
1Stem Cell Biochemistry Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Nature communications
|July 26, 2023
概括
一个新发现的途径使用泛素酶CRL3-KLHL4来抑制CDC42信号传递,这对于面部,大脑和皮肤的胚胎发育至关重要.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 确切的分子机制控制胚胎外皮模式进入神经,表皮和面血统仍然难以捉摸.
- 了解这些过程对于理解影响面部和神经发育的先天性疾病至关重要.
研究的目的:
- 阐明调节脊椎动物头部早期外皮分化的翻译后途径.
- 在胚胎发育过程中确定协调细胞命运决策的关键分子参与者.
主要方法:
- 生物化学疾病变异分析,以确定调节途径.
- 分析CRL3-KLHL4泛素酶及其与CDC42信号元件的相互作用.
- 调查PAK1无处不在及其功能后果.
主要成果:
- CRL3-KLHL4通过单双化PAK1来限制CDC42的信号传递,将其转化为CDC42抑制剂.
- 丢失CRL3-KLHL4或与疾病相关的KLHL4变异会损害PAK1的无处不在,导致CDC42过度激活.
- 在没有适当的CRL3-KLHL4功能的情况下观察到有缺陷的外皮外纹和神经元.
结论:
- 在脊椎动物头部发育过程中,限制CDC42信号传递的依赖于无处不在的机制是必不可少的.
- 这条途径协调细胞命运的决定和形态遗传变化,以便进行适当的器官生成.
- 这种途径的失调有助于面和神经结构的发育缺陷.
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