Jiraiya Attenuates BMP Signaling by Interfering with Type II BMP Receptors in Neuroectodermal Patterning
Jiraiya Attenuates BMP Signaling by Interfering with Type II BMP Receptors in Neuroectodermal Patterning
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DOI：
10.1016/j.devcel.2010.09.001
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发表时间：
2010-10-19
影响因子：
11.8
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
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作者：
Aramaki, Toshihiro;Sasai, Noriaki;Sasai, Yoshiki
在胚胎发生过程中，骨形态发生蛋白（BMP）信号需要以局部受限的方式精细调节。在这里，我们报告了一种由膜蛋白Jiraiya执行的BMP反应控制的细胞内在模式。在Xeno pus胚胎中，仅在神经外胚层表达的合子Jiraiya对于限制依赖于BMP信号的背神经发育至关重要。在动物帽实验中，Jiraiya选择性地和细胞自主地抑制BMP信号，而Jiraiya的敲低增强了信号传导。在细胞中，Jiraiya选择性地与II型BMP受体（BMPRII）形成复合物，并下调功能性BMPRII的细胞表面定位。这种与Jiraiya的功能相互作用依赖于BMPRII独特的尾结构域，特别是保守的EVNNNG基序，其功能尚不清楚。因此，Jiraiya代表了一种细胞内在的切断机制，通过亚型选择受体控制对BMP信号的动态响应。
During embryogenesis, bone morphogenetic protein (BMP) signaling needs to be finely tuned in a locally restricted manner. Here, we report a cell-intrinsic mode of BMP response control executed by the membrane protein Jiraiya. In the Xeno pus embryo, zygotic Jiraiya, expressed exclusively in the neuroectoderm, is essential and sufficient for limiting dorsal neural development, which is dependent on BMP signals. In animal cap assays, Jiraiya selectively and cell-autonomously inhibits BMP signaling, while Jiraiya's knockdown enhances the signaling. In the cell, Jiraiya selectively forms a complex with type II BMP receptor (BMPRII) and downregulates the cell surface localization of functional BMPRII. This functional interaction with Jiraiya depends on the unique tail domain of BMPRII, and, in particular, the conserved EVNNNG motif, the function of which has been unknown. Thus, Jiraiya represents a cell-intrinsic cutoff mechanism for dynamic responsiveness to BMP signals via subtype-selective receptor control.