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赛马福林受体通过β-catenin降解来对抗Wnt信号传输
Tyler M Hoard1, Katie Liu1, Kenneth M Cadigan2
1Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
bioRxiv : the preprint server for biology
|June 10, 2024
概括
赛马福林 (SEMA) 受体,神经皮林 (NRP) 和plexin (PLXN),对抗Wnt信号传递. 删除这些受体会增加Wnt通路的活性,揭示它们在控制发育过程中的细胞反应中的作用.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 分子生物学分子生物学
背景情况:
- 精确控制形态原信号传递对于适当的胚胎发育至关重要.
- 半素 (SEMA) 受体,包括神经素 (NRPs) 和plexin (PLXNs),已知是对 Hedgehog (HH) 信号的积极调节者.
- 确保正确的形态原活性和细胞反应的机制仍然是积极研究的领域.
研究的目的:
- 为了研究赛马福林 (SEMA) 受体,特别是神经皮林 (NRP) 和plexin (PLXN) 在调节Wnt信号传递中的作用.
- 阐明SEMA受体影响Wnt通路活性的分子机制.
- 为了确定SEMA受体介导的Wnt对抗性是否依赖于初级毛.
主要方法:
- 用纤维细胞和上皮细胞进行实验.
- 进行了基因删除研究 (纤维细胞中的NRp1/2删除).
- 研究的下游信号组件包括Dishevelled (DVL) 和β-catenin (CTNNB1).
- 评估了蛋白酶依赖性降解和GSK3β/CK1激酶活性.
主要成果:
- 发现NRPs和PLXNs在两种细胞类型中对抗Wnt信号传递.
- 删除Nrp1/2导致基线Wnt通路活性增加和对Wnt刺激的反应增强.
- 通过SEMA受体介导的Wnt对抗性独立于初级毛,与其在HH信号传递中的作用不同.
- PLXN和NRP通过DVL的下游依赖蛋白酶体的机制破坏β-catenin (CTNNB1) 的稳定.
- NRPs,但不是PLXNs,以GSK3β/CK1依赖的方式对抗Wnt信号.
结论:
- SEMA受体 (NRP和PLXN) 作为Wnt信号通路的新对手.
- 这些受体在Wnt信号抑制中发挥着不同的作用,NRP表现出酶依赖活性.
- 赛马受体可以整合来自多个途径的信号,在发育过程中影响更广泛的细胞功能.
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