Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
Dev Cell. 2010 Oct 19;19(4):547-61. doi: 10.1016/j.devcel.2010.09.001.
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 Xenopus 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.
在胚胎发生过程中,骨形态发生蛋白(BMP)信号需要以局部限制的方式进行精细调节。在这里,我们报告了一种由膜蛋白 Jiraiya 执行的细胞内在的 BMP 反应控制模式。在非洲爪蟾胚胎中,仅在神经外胚层中表达的合子 Jiraiya 对于限制依赖于 BMP 信号的背侧神经发育是必需和充分的。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。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 的独特尾部结构域,特别是保守的 EVNNNG 基序,其功能尚不清楚。因此,Jiraiya 代表了一种通过亚类选择性受体控制对 BMP 信号进行动态响应的细胞内在截止机制。