在毛处平滑的PKA抑制转化了 Hedgehog信号
bioRxiv : the preprint server for biology
|April 16, 2025
概括
刺 (HH) 信号依赖于Smo (SMO) 抑制内蛋白激酶A (PKA). 这项研究证实SMO直接抑制状PKA,这是HH通路激活的关键步骤.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 刺 (HH) 信号传递对于脊椎动物的发育至关重要,由主要皮介导.
- 乳毛中的光滑 (SMO) 丰富是关键事件,导致GLI蛋白激活.
- 最近的发现表明,SMO抑制蛋白激酶A (PKA),但其在乳毛中的作用仍然不清楚.
研究的目的:
- 调查SMO是否特别抑制PKA在初级毛内激活HH信号传导通路.
- 阐明SMO在HH信号传递过程中调节PKA活动的机制.
主要方法:
- 开发一种新的毛PKA生物传感器,以精确测量初级毛中的PKA活性.
- 使用Sonic hedgehog (SHH) 和SMO激动剂 (SAG) 来激活HH通路.
- 使用基因操纵,包括SMO的突变和GRK2/3的抑制,以剖析信号机制.
主要成果:
- 通过SHH或SAG激活HH通路导致状PKA活动的显著抑制.
- 通过GRK2/3阻断SMO的酸化,取消了SMO抑制状PKA的能力.
- 在SMO C端尾伪基质位点的干扰损害了SMO介导的PKA抑制.
- 发现Gαi对于SMO抑制状PKA的作用是不可或缺的.
结论:
- HH信号转导是直接通过SMO-依赖的抑制直接介导的PKA在主要的毛.
- 这种抑制机制依赖于GRK2/3并涉及SMO C终端尾部.
- 这些发现提供了SMO活动和HH信号中的PKA调节之间的机制联系.
相关概念视频
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
Microtubules in Signaling
1.7K
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
1.7K
Notch Signaling Pathway
4.1K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.1K
The JAK-STAT Signaling Pathway
8.4K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.4K
Mechanism of Ciliary Motion
3.5K
The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
3.5K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.0K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.0K


