A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss).
A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss).
复制标题
DOI：
10.1038/srep28969
复制
发表时间：
2016-07-04
影响因子：
4.6
通讯作者：
Våge DI
中科院分区：
文献类型：
--
作者：
Khan UW;Øverli Ø;Hinkle PM;Pasha FA;Johansen IB;Berget I;Silva PI;Kittilsen S;Höglund E;Omholt SW;Våge DI
在许多脊椎动物物种中，可见的基于黑色素的色素沉着模式与高应激和抗病性相关，但这种性状关联的近似机制仍然是个谜。在这里，我们表明，在一个经典的色素沉着基因，黑素细胞刺激激素受体（MC1R）的错义突变，强烈相关的类固醇黑皮质素2受体（MC2R）的mRNA表达之间的显着差异高（HR）和低响应（LR）虹鳟鱼（虹鳟鱼mykiss）。我们还通过实验表明，皮质醇植入物增加了皮肤中agglutinin信号蛋白（ASIP）mRNA的表达，这可能解释了HR特征与皮肤黑色素图案减少之间的关联。分子动力学模拟预测，MC 2 R功能所需的黑皮质素2受体辅助蛋白（MRAP）与两种MC 1 R变体的结合方式不同。考虑到MC2R和MC1R变体的mRNA存在于头肾细胞中，我们假设MC2R活性部分由MC1R变体对MRAP的不同结合亲和力调节。在哺乳动物细胞中的实验证实，鳟鱼MRAP与两种鳟鱼MC1R变体和MC2R相互作用，但未能检测到MC2R信号转导的调节，可能是由于高组成性MC1R活性。
In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity.