Dept. of Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
Dept. of Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Biochem Biophys Res Commun. 2019 Sep 10;517(1):23-28. doi: 10.1016/j.bbrc.2019.06.133. Epub 2019 Jul 23.
Semaphorins are a large and important family of signaling molecules conserved in Bilateria. An important determinant of the biological function of their largest class, the secreted class 3 semaphorins, is the specificity of their binding to neuropilins, a key component of a larger holoreceptor complex. We compared these binding specificities in mice and zebrafish, species whose most recent common ancestor was more than 400 million years in the past. We also compared the binding specificities of zebrafish class 3 semaphorins that were duplicated very early within the teleost lineage. We found a surprising conservation of neuropilin binding specificities when comparing both paralogous zebrafish semaphorin pairs and orthologous zebrafish and mouse semaphorin pairs. This finding was further supported by a remarkable conservation of binding specificities in cross-species pairings of semaphorins and neuropilins. Our results suggest that the qualitative specificities with which particular semaphorins bind to particular neuropilins has remained nearly invariant over approximately 400 million years of evolution.
神经信号蛋白是两侧对称动物中一个庞大而重要的信号分子家族。它们最大的一类分泌型 3 类神经信号蛋白的生物学功能的一个重要决定因素是其与神经纤毛蛋白特异性结合，神经纤毛蛋白是更大的全受体复合物的关键组成部分。我们比较了在过去 4 亿多年的时间里，亲缘关系最近的老鼠和斑马鱼的这些结合特异性。我们还比较了在硬骨鱼支系中非常早期重复的斑马鱼 3 类神经信号蛋白的结合特异性。当比较斑马鱼神经信号蛋白的同源和异源对以及与其平行的神经信号蛋白对时，我们发现神经纤毛蛋白结合特异性惊人地保守。这一发现进一步得到了跨物种神经信号蛋白和神经纤毛蛋白配对结合特异性的显著保守性的支持。我们的研究结果表明，在大约 4 亿年的进化过程中，特定的神经信号蛋白与特定的神经纤毛蛋白结合的定性特异性几乎保持不变。
