Functional conservation of the apoptotic machinery from coral to man: the diverse and complex Bcl-2 and caspase repertoires of Acropora millepora
Functional conservation of the apoptotic machinery from coral to man: the diverse and complex Bcl-2 and caspase repertoires of Acropora millepora
复制标题
从珊瑚到人类的细胞凋亡机制的功能保护：千叶鹿角珊瑚多样化且复杂的 Bcl-2 和 caspase 库
作者：
A. Moya;K. Sakamaki;Benjamin M. Mason;L. Huisman;S. Forêt;Y. Weiss;Tara E. Bull;K. Tomii;K. Imai;D. Hayward;E. Ball;David J. Miller
细胞凋亡是后生动物普遍存在的特征，但其进化起源尚不清楚。虽然小杆线虫和果蝇在建立细胞凋亡的分子基础方面发挥了关键作用，但现在很清楚，这些动物的细胞死亡途径并不反映祖先的特征。相反，最近的工作表明，细胞凋亡的刺胞动物的网络可能是复杂的和脊椎动物样的，因此表征的细胞凋亡的补充的代表的基础刺胞动物类珊瑚虫将有助于我们了解脊椎动物的细胞凋亡network.ResultsWe的进化描述的Bcl-2和caspase蛋白库的珊瑚鹿角珊瑚millepora，利用全面的转录组学数据可用于这个物种。分子生物学研究表明，一些鹿角珊瑚蛋白是特定的哺乳动物促凋亡Bcl-2家族成员的直系同源物，但其他Bcl-2和半胱天冬酶的关系尚不清楚。珊瑚Bcl-2蛋白的促或抗凋亡活性通过在哺乳动物细胞中的表达进行了研究，结果表明，尽管抗凋亡Bcl-2蛋白的序列保守性有限，但效应器/抗凋亡机制的功能保守性。在鹿角珊瑚中发现了一种新的半胱天冬酶类型（“半胱天冬酶-X”），含有非活性和活性半胱天冬酶结构域，似乎仅限于珊瑚。当在哺乳动物细胞中表达时，全长半胱天冬酶-X导致活力丧失，并且仅含有活性结构域的截短版本在诱导细胞死亡方面更有效，这表明非活性结构域可能调节全长蛋白的活性。结构预测表明，caspase-X中的活性和非活性caspase结构域可能相互作用，导致结构类似于半胱天冬酶原-8中的活性结构域和哺乳动物c-FLIP抗-凋亡因子。结论这里提供的数据证实，许多基本的机制涉及的内在和外在的凋亡途径是在地方共同祖先的刺胞动物两侧对称随着大多数或所有的剧目的珊瑚Bcl-2和半胱天冬酶的鉴定，我们的研究结果不仅提供了新的观点，对凋亡途径的演变，但也为未来的实验研究走向一个完整的理解珊瑚漂白机制的框架，其中凋亡细胞死亡可能参与。
BackgroundApoptotic cell death is a defining and ubiquitous characteristic of metazoans, but its evolutionary origins are unclear. Although Caenorhabditis and Drosophila played key roles in establishing the molecular bases of apoptosis, it is now clear that cell death pathways of these animals do not reflect ancestral characteristics. Conversely, recent work suggests that the apoptotic networks of cnidarians may be complex and vertebrate-like, hence characterization of the apoptotic complement of representatives of the basal cnidarian class Anthozoa will help us to understand the evolution of the vertebrate apoptotic network.ResultsWe describe the Bcl-2 and caspase protein repertoires of the coral Acropora millepora, making use of the comprehensive transcriptomic data available for this species. Molecular phylogenetics indicates that some Acropora proteins are orthologs of specific mammalian pro-apoptotic Bcl-2 family members, but the relationships of other Bcl-2 and caspases are unclear. The pro- or anti-apoptotic activities of coral Bcl-2 proteins were investigated by expression in mammalian cells, and the results imply functional conservation of the effector/anti-apoptotic machinery despite limited sequence conservation in the anti-apoptotic Bcl-2 proteins. A novel caspase type (“Caspase-X”), containing both inactive and active caspase domains, was identified in Acropora and appears to be restricted to corals. When expressed in mammalian cells, full-length caspase-X caused loss of viability, and a truncated version containing only the active domain was more effective in inducing cell death, suggesting that the inactive domain might modulate activity in the full-length protein. Structure prediction suggests that the active and inactive caspase domains in caspase-X are likely to interact, resulting in a structure resembling that of the active domain in procaspase-8 and the inactive caspase domain in the mammalian c-FLIP anti-apoptotic factor.ConclusionsThe data presented here confirm that many of the basic mechanisms involved in both the intrinsic and extrinsic apoptotic pathways were in place in the common ancestor of cnidarians and bilaterians. With the identification of most or all of the repertoires of coral Bcl-2 and caspases, our results not only provide new perspectives on the evolution of apoptotic pathways, but also a framework for future experimental studies towards a complete understanding of coral bleaching mechanisms, in which apoptotic cell death might be involved.
DOI：
10.1042/bj20101738
发表时间：
2011-02-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Pop C;Oberst A;Drag M;Van Raam BJ;Riedl SJ;Green DR;Salvesen GS
通讯作者：
Salvesen GS
影响因子：
2.9
作者：
Zhou, Q;Krebs, JF;Salvesen, GS
通讯作者：
Salvesen, GS