Structural and functional evidences for a type 1 TGF-β sensu stricto receptor in the lophotrochozoan Crassostrea gigas suggest conserved molecular mechanisms controlling mesodermal patterning across bilateria

Structural and functional evidences for a type 1 TGF-β sensu stricto receptor in the lophotrochozoan Crassostrea gigas suggest conserved molecular mechanisms controlling mesodermal patterning across bilateria
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DOI:
10.1016/j.mod.2004.12.004
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发表时间:
2005-05-01
影响因子:
2.6
通讯作者:
Cunningham, C
Cunningham, C
中科院分区:
生物学4区
文献类型:
--
作者:
Herpin, A;Lelong, C;Cunningham, C

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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.)。这些配体已被证明在许多生物过程中发挥关键作用,包括早期胚胎发育和免疫调节。它们通过 I 型和 II 型受体的异聚复合物转导信号。此类受体已在蜕皮动物中被发现,但在另一个主要的原生口进化枝,即轮轮动物中尚未发现。在这里,我们报告了第一个冠轮动物 TGF beta s.s. 的鉴定。来自软体动物巨牡蛎的 I 型受体(Cg-TGF beta RI)。系统发育和结构分析以及早期发育期间的表达模式表明 Cg-TGF beta RI 属于 TGF beta s.s./激活素 I 型受体进化枝,功能研究证实了这些推论。使用斑马鱼胚胎作为报告生物体表明,Cg-TGF beta RI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,会由于腹外侧中胚层模式的强烈调节而导致一系列表现出严重前后模式紊乱的表型。最后,在体内细菌 LPS 攻击期间,通过血细胞和外套膜边缘的实时 PCR 研究了 C. gigas 免疫调节过程中的 Cg-TGF beta RI 细胞因子活性。这项研究的一个证据表明,控制中胚层模式和所有两侧对称动物的一些免疫调节的分子机制可以通过功能性 TGF-β s.s 来保存。冠轮动物中的途径。 (c) 2004 Elsevier Ireland Ltd. 保留所有权利。
The transforming growth factor beta (TGF beta) superfamily includes bone morphogenetic proteins, activins and TGF-beta sensu stricto (s.s.). These ligands have been shown to play a key role in numerous biological processes including early embryonic development and immune regulation. They transduce their signal through a hetromeric complex of type I and type II receptors. Such receptors have been identified in ecdysozoans but none have been found as yet in the other major protostomal clade, the lophotrochozoans. Here, we report the identification of the first lophotrochozoan TGF beta s.s. type I receptor (Cg-TGF beta RI) from the mollusk Crassostrea gigas. The phylogenetic and structural analyses as well as the expression pattern during early development suggest Cg-TGF beta RI to belong to the TGF beta s.s./activin type I receptor clade and functional studies corroborate these deductions. The use of the zebrafish embryo as a reporter organism reveals that either Cg-TGF beta RI or its dominant negative acting truncated form, when overexpressed during gastrulation, resulted in a range of phenotypes displaying severe disturbance of anterioposterior patterning due to a strong modulation of ventrolateral mesoderm patterning. Finally, a Cg-TGF beta RI cytokine activity during immune regulation in C. gigas has been investigated by real-time PCR in haemocytes and mantle edge during an in vivo bacterial LPS challenge. One piece of evidence from this study suggests that the molecular mechanisms controlling mesodermal patterning and some immune regulations across all bilateria could be conserved through a functional TGF-beta s.s. pathway in lophotrochozoans. (c) 2004 Elsevier Ireland Ltd. All rights reserved.