Local protease signaling contributes to neural tube closure in the mouse embryo.
Local protease signaling contributes to neural tube closure in the mouse embryo.
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DOI：
10.1016/j.devcel.2009.11.014
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发表时间：
2010-01-19
影响因子：
11.8
通讯作者：
Coughlin, Shaun R.
中科院分区：
文献类型：
--
作者：
Camerer, Eric;Barker, Adrian;Duong, Daniel N.;Ganesan, Rajkumar;Kataoka, Hiroshi;Cornelissen, Ivo;Darragh, Molly R.;Hussain, Arif;Zheng, Yao-Wu;Srinivasan, Yoga;Brown, Christopher;Xu, Shan-Mei;Regard, Jean B.;Lin, Chen-Yong;Craik, Charles S.;Kirchhofer, Daniel;Coughlin, Shaun R.
我们报告了一个意想不到的作用，蛋白酶信号在神经管关闭和中枢神经系统的形成。缺乏蛋白酶激活受体1和2的小鼠胚胎表现为后脑和后神经孔关闭缺陷，并发生脑畸形和脊柱裂，这是人类重要的先天性异常。Par1和Par2在表面外胚层表达，Par2选择性地沿闭合线表达。在这些par2表达细胞中，Gi/z和Rac1功能的消融破坏了神经管闭合，进一步暗示了G蛋白偶联受体，并确定了可能的效应途径。蛋白酶和Par2表达模式的聚类分析显示，一组膜系定蛋白酶经常与Par2共表达。其中基质酶以皮摩尔效激活Par2，肝蛋白酶和前列腺蛋白酶激活基质酶。总之，我们的研究结果提示了蛋白酶激活受体信号在神经管闭合中的作用，并确定了在这种情况下可能触发Par2信号并监测和调节上皮完整性的局部蛋白酶网络。
We report an unexpected role for protease signaling in neural tube closure and formation of the central nervous system. Mouse embryos lacking protease-activated receptor 1 and 2 showed defective hindbrain and posterior neuropore closure and developed exencephaly and spina bifida, important human congenital anomalies. Par1 and Par2 were expressed in surface ectoderm, Par2 selectively along the line of closure. Ablation of Gi/z and Rac1 function in these Par2-expressing cells disrupted neural tube closure, further implicating G protein-coupled receptors and identifying a likely effector pathway. Cluster analysis of protease and Par2 expression patterns revealed a group of membrane-tethered proteases often co-expressed with Par2. Among these, matriptase activated Par2 with picomolar potency, and hepsin and prostasin activated matriptase. Together, our results suggest a role for protease-activated receptor signaling in neural tube closure and identify a local protease network that may trigger Par2 signaling and monitor and regulate epithelial integrity in this context.
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DOI：
10.1084/jem.20082242
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Briot A;Deraison C;Lacroix M;Bonnart C;Robin A;Besson C;Dubus P;Hovnanian A
通讯作者：
Hovnanian A
影响因子：
50.3
作者：
Klezovitch, O;Chevillet, J;Vasioukhin, V
通讯作者：
Vasioukhin, V
影响因子：
64.8
作者：
Connolly, AJ;Ishihara, H;Coughlin, SR
通讯作者：
Coughlin, SR
影响因子：
6.5
作者：
Hansson, L;Bäckman, A;Egelrud, T
通讯作者：
Egelrud, T
影响因子：
4.8
作者：
Camerer, E;Kataoka, H;Coughlin, SR
通讯作者：
Coughlin, SR