Structural and functional evidence for a singular repertoire of BMP receptor signal transducing proteins in the lophotrochozoan Crassostrea gigas suggests a shared ancestral BMP/activin pathway
Structural and functional evidence for a singular repertoire of BMP receptor signal transducing proteins in the lophotrochozoan Crassostrea gigas suggests a shared ancestral BMP/activin pathway
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DOI：
10.1111/j.1742-4658.2005.04761.x
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发表时间：
2005-07-01
期刊：
影响因子：
5.4
通讯作者：
Cunningham, C
中科院分区：
文献类型：
--
作者：
Herpin, A;Lelong, C;Cunningham, C
转化生长因子 β (TGF-β) 超家族包括骨形态发生蛋白、激活素和 TGF-β sensu stricto (s.s)。这些配体通过 I 型和 II 型受体的异聚复合物转导信号，已被证明在许多生物过程中发挥关键作用，包括后口动物和蜕皮动物的早期胚胎发育。冠足动物是两侧对称动物的第三大类群，一直处于后生动物发育分子研究的背景中。我们报告了双壳类软体动物巨牡蛎 BMP 通路机制核心部分（Cg-BMPR1 I 型受体和 Cg-TGF beta sfR2 II 型受体）的克隆和功能研究，显示了该超家族不寻常的信号转导功能模式。使用斑马鱼胚胎作为报告生物体表明，Cg-BMPR1、Cg-TGF beta sfR2、Cg-ALR I（一种激活素 I 型受体）或其显性负作用截短形式在原肠胚形成过程中过度表达时，由于腹外侧中胚层模式的强烈调节，导致一系列表现出前后模式严重紊乱的表型。结果表明，Cg-BMPR1 以及一定程度上的 Cg-TGF beta sfR2 蛋白在 C. gigas 中的功能与其斑马鱼直系同源物类似。最后，基于系统发育分析，我们提出了完整 TGF-β 超家族的进化模型。因此，本研究提供的证据表明，螺旋虫中可能存在通过祖先 BMP/激活素途径保守的内中胚层/外中胚层诱导机制，其中单一、混杂且可能独特的 Cg-TGF beta sfR2 将是 BMP 和激活素配体共享的 II 型受体界面。
The transforming growth factor beta (TGF-beta) superfamily includes bone morphogenetic proteins, activins and TGF-beta sensu stricto (s.s). These ligands, which transduce their signal through a heteromeric complex of type I and type II receptors, have been shown to play a key role in numerous biological processes including early embryonic development in both deuterostomes and ecdyzozoans. Lophochotrozoans, the third major group of bilaterian animals, have remained in the background of the molecular survey of metazoan development. We report the cloning and functional study of the central part of the BMP pathway machinery in the bivalve mollusc Crassostrea gigas (Cg-BMPR1 type I receptor and Cg-TGF beta sfR2 type II receptor), showing an unusual functional mode of signal transduction for this superfamily. The use of the zebrafish embryo as a reporter organism revealed that Cg-BMPR1, Cg-TGF beta sfR2, Cg-ALR I, an activin Type I receptor or their dominant negative acting truncated forms, when overexpressed during gastrulation, resulted in a range of phenotypes displaying severe disturbance of anterioposterior patterning, due to strong modulations of ventrolateral mesoderm patterning. The results suggest that Cg-BMPR1, and to a certain degree Cg-TGF beta sfR2 proteins, function in C. gigas in a similar way to their zebrafish orthologues. Finally, based on phylogenetic analyses, we propose an evolutionary model within the complete TGF-beta superfamily. Thus, evidence provided by this study argues for a possible conserved endomesoderm/ectomesoderm inductive mechanism in spiralians through an ancestral BMP/activin pathway in which the singular, promiscuous and probably unique Cg-TGF beta sfR2 would be the shared type II receptor interface for both BMP and activin ligands.