状G蛋白结合受体Gpr161通过cAMP信号传递负面调节Sonic刺通路
Saikat Mukhopadhyay1, Xiaohui Wen, Navneet Ratti
1Department of Research Oncology, Genentech Inc., South San Francisco, CA 94080, USA. saikat.mukhopadhyay@utsouthwestern.edu
Cell
|January 22, 2013
概括
与G蛋白结合的受体Gpr161对于Sonic hedgehog (Shh) 信号调节在初级眼中至关重要. 它的损失增加了SHH信号,影响了神经管的发育.
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:
- 主性皮对于脊椎动物的Sonic hedgehog (Shh) 信号传输至关重要.
- 矛盾的是,肌内运输复合体A (IFT-A) 的突变会增加SHH信号.
- IFT-A将类似于体的蛋白 Tulp3 引入眼.
研究的目的:
- 确定涉及到Shh信号调节的新型组件在初级眼.
- 研究Gpr161在Tulp3/IFT-A-依赖的状细胞局部化和Shh通路调节中的作用.
主要方法:
- 使用了具有Gpr161.1.遗传损失的小鼠模型.
- 分析了Gpr161与Tulp3和IFT-A.A.相关的初级眼局部.
- 评估了Gpr161突变体中的Shh信号通路活性和Gli3处理.
- 测量了周期性AMP (cAMP) 水平和Gpr161从小内化.
主要成果:
- Gpr161以Tulp3/IFT-A-依赖的方式定位到初级眼.
- 在小鼠中完全失去Gpr161导致妊娠中期的死亡率和神经管Shh信号的升高,模仿Tulp3/IFT-A突变.
- 活性Gpr161提升cAMP,通过促进Gli3抑制剂形式抑制Shh信号.
- SHH信号诱导Gpr161从乳内部化,抑制其活动.
结论:
- Gpr161是主要的调节器Shh信号在初级毛.
- Gpr161作为一种维护的脊椎动物G蛋白合受体,对神经管发育至关重要.
- 通过cAMP调节和Gli3处理,Gpr161定义了一条连接蛋白激酶A激活到Shh信号的途径.
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