受体Allostery在胚胎发育过程中促进了上下文依赖的声波刺信号
Shariq S Ansari1, Miriam E Dillard1, Mohamed Ghonim2
1Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
bioRxiv : the preprint server for biology
|February 20, 2025
概括
在胚胎发育过程中,与SMO结合的阿拉基酸 (AA) 对Sonic Hedgehog (SHH) 途径活性至关重要. 破坏这种结合会导致小鼠患有严重的心脏和肺部缺陷.
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:
- 声波刺 (SHH) 信号传输对于胚胎发育至关重要,可以在各种组织中形成模式.
- 信号传感器Smoothened (SMO) 是由包括醇,氧醇和酸 (AA) 在内的配体激活的.
- 在体外研究中,通过组合性连接体结合的SMO的体调节被建议,但体内证据缺乏.
研究的目的:
- 为了研究酸 (AA) 结合在平滑化 (SMO) 性调节中的体内作用.
- 为了阐明在胚胎发生过程中被破坏的AA与SMO结合的功能后果.
- 确定受损的SMO-AA相互作用对SHH通路活性和组织发育的影响.
主要方法:
- 在SMO的7跨膜 (7TM) 捆内映射一个AA结合口袋.
- 产生和分析一个具有AA与SMO结合性损害的Knockin小鼠模型.
- 在突变小鼠中评估SHH通路诱导和发育表型.
主要成果:
- 破坏AA结合口袋减弱了SHH和醇刺激的SMO诱导.
- 同性异体突变小鼠表现出色,高围产死亡率和先天性心脏病.
- 幸存的突变动物表现出肺部发育不良和发育不良,而神经发育仍然不受影响.
结论:
- 阿拉基酸 (AA) 与SMO结合对于SHH通路活化在体内至关重要.
- 通过AA对SMO的上下文依赖的全调节对于适当的心肺发育至关重要.
- 受损的SMO-AA相互作用导致严重的发育缺陷,突出显示了该途径在心脏和肺形成中的作用.
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