NR3E receptors in cnidarians: A new family of steroid receptor relatives extends the possible mechanisms for ligand binding.
NR3E receptors in cnidarians: A new family of steroid receptor relatives extends the possible mechanisms for ligand binding.
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DOI：
10.1016/j.jsbmb.2018.06.014
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Markov GV
中科院分区：
文献类型：
--
作者：
Khalturin K;Billas IML;Chebaro Y;Reitzel AM;Tarrant AM;Laudet V;Markov GV
类固醇激素受体是两侧对称动物发育和生理的重要调节因子，但类固醇信号在刺胞动物中的作用一直存在争议。刺胞动物产生类固醇，包括带有侧链的A环芳香族类固醇，但这些类固醇可能是通过与脊椎动物制造A环芳香族类固醇的途径不同的途径制造的。在这里，我们提出了比较基因组分析表明存在一个以前未描述的核受体家族内的水母刺胞动物，我们建议称之为NR 3E。该家族早于双边动物中ERR/ER/SR的多样化，表明第一个NR 3进化于盾板动物和刺胞动物双边动物的共同祖先，在珊瑚动物中具有谱系特异性损失，即使该谱系中的多个物种已被证明产生芳香族类固醇，其功能仍不清楚。我们偶然发现，转基因水螅表皮细胞内的细胞质因子可以触发异源表达的人ERα的核转位。这使我们假设芳香族类固醇也可能存在于水母类刺胞动物谱系中，包括水螅，并可能解释人类ERα的易位。对雌激素A（一种刺胞动物A环芳香族类固醇）与水螅NR 3E的配体结合口袋的对接实验表明，如果芳香族类固醇确实是真正的配体（这还有待证明），它将通过与雌二醇结合脊椎动物ER的方式部分不同的机制与口袋结合。
Steroid hormone receptors are important regulators of development and physiology in bilaterian animals, but the role of steroid signaling in cnidarians has been contentious. Cnidarians produce steroids, including A-ring aromatic steroids with a side-chain, but these are probably made through pathways different than the one used by vertebrates to make their A-ring aromatic steroids. Here we present comparative genomic analyses indicating the presence of a previously undescribed nuclear receptor family within medusozoan cnidarians, that we propose to call NR3E. This family predates the diversification of ERR/ER/SR in bilaterians, indicating that the first NR3 evolved in the common ancestor of the placozoan and cnidarian-bilaterian with lineage-specific loss in the anthozoans, even though multiple species in this lineage have been shown to produce aromatic steroids, whose function remain unclear. We discovered serendipitously that a cytoplasmic factor within epidermal cells of transgenic Hydra vulgaris can trigger the nuclear translocation of heterologously expressed human ERα. This led us to hypothesize that aromatic steroids may also be present in the medusozoan cnidarian lineage, which includes Hydra, and may explain the translocation of human ERα. Docking experiments with paraestrol A, a cnidarian A-ring aromatic steroid, into the ligand-binding pocket of Hydra NR3E indicates that, if an aromatic steroid is indeed the true ligand, which remains to be demonstrated, it would bind to the pocket through a partially distinct mechanism from the manner in which estradiol binds to vertebrate ER.
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影响因子：
4.1
作者：
Edison AS;Hall RD;Junot C;Karp PD;Kurland IJ;Mistrik R;Reed LK;Saito K;Salek RM;Steinbeck C;Sumner LW;Viant MR
通讯作者：
Viant MR
DOI：
10.1073/pnas.94.13.6803
发表时间：
1997-06-24
影响因子：
11.1
作者：
Escriva, H;Safi, R;Laudet, V
通讯作者：
Laudet, V
影响因子：
1.2
作者：
HAND, C;UHLINGER, KR
通讯作者：
UHLINGER, KR
影响因子：
2.7
作者：
Gauchat, D;Escriva, H;Galliot, B
通讯作者：
Galliot, B
DOI：
10.1016/j.bbrc.2008.08.047
发表时间：
2008-10-31
影响因子：
3.1
作者：
Baker, Michael E.
通讯作者：
Baker, Michael E.