A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia.
A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia.
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DOI：
10.1016/j.devcel.2012.07.004
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发表时间：
2012-10-16
影响因子：
11.8
通讯作者：
Rohatgi, Rajat
中科院分区：
文献类型：
--
作者：
Dorn, Karolin V.;Hughes, Casey E.;Rohatgi, Rajat
脊椎动物Hedgehog(HH)信号是由配体触发的纤毛膜中Smomoothens(Smo)的积聚而在初生纤毛启动的。潜在的生化机制仍不清楚。我们发现，HH激动剂促进了Smo和Evc2之间的联系，Evc2是一种纤毛蛋白，在两种人类纤毛疾病中存在缺陷。Smo-Evc2复合体的形成受到严格的空间控制，仅限于一个不同的睫状室，即EVC区。突变的Evc2蛋白定位在纤毛中，但从EVC区移位，是HH信号的主要抑制因子。禁用Evc2功能会在Smo与下游调节蛋白激酶A和融合抑制因子之间的特定步骤阻断HH信号，阻止Gli转录因子的激活。我们的数据表明，EVC区的Smo-Evc2信号复合体是HH信号传递所必需的，并阐明了两种人类纤毛疾病的分子基础。
Vertebrate Hedgehog (Hh) signaling is initiated at primary cilia by the ligand-triggered accumulation of Smoothened (Smo) in the ciliary membrane. The underlying biochemical mechanisms remain unknown. We find that Hh agonists promote the association between Smo and Evc2, a ciliary protein that is defective in two human ciliopathies. The formation of the Smo-Evc2 complex is under strict spatial control, being restricted to a distinct ciliary compartment, the EvC zone. Mutant Evc2 proteins that localize in cilia but are displaced from the EvC zone are dominant inhibitors of Hh signaling. Disabling Evc2 function blocks Hh signaling at a specific step between Smo and the downstream regulators protein kinase A and Suppressor of Fused, preventing activation of the Gli transcription factors. Our data suggest that the Smo-Evc2 signaling complex at the EvC zone is required for Hh signal transmission and elucidate the molecular basis of two human ciliopathies.
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影响因子：
--
作者：
Goetz, Sarah C.;Ocbina, Polloneal J. R.;Anderson, Kathryn V.
通讯作者：
Anderson, Kathryn V.
影响因子：
3.8
作者：
Galdzicka, M;Patnala, S;Ginns, EI
通讯作者：
Ginns, EI
影响因子：
21.3
作者：
Chih, Ben;Liu, Peter;Peterson, Andrew S.
通讯作者：
Peterson, Andrew S.
影响因子：
56.9
作者：
Rohatgi, Rajat;Milenkovic, Ljiljana;Scott, Matthew P.
通讯作者：
Scott, Matthew P.
DOI：
10.1083/jcb.201006105
发表时间：
2010-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Craige B;Tsao CC;Diener DR;Hou Y;Lechtreck KF;Rosenbaum JL;Witman GB
通讯作者：
Witman GB