Shu Chang, Wang Shanchen, Xu Tianjun
Laboratory of Fish Biogenetics & Immune Evolution, College of Marine Science, Zhejiang Ocean University, Zhoushan 316022, China.
Laboratory of Fish Biogenetics & Immune Evolution, College of Marine Science, Zhejiang Ocean University, Zhoushan 316022, China.
Dev Comp Immunol. 2015 May;50(1):19-25. doi: 10.1016/j.dci.2015.01.004. Epub 2015 Jan 13.
Dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN/CD209) and liver/lymph node-specific ICAM-grabbing non-integrin (L-SIGN/CD299) which are homologues of DC-SIGN are important members in C-type lectin receptors family as key molecules to recognize and eliminate pathogens in the innate immune system. DC-SIGN and L-SIGN have become hot topics in recent studies which both served as cell adhesion and phagocytic pathogen recognition receptors in mammals. However, there have been almost no studies of DC-SIGN and L-SIGN structure and characters in fish, only DC-SIGN in the zebrafish had been studied. In our study, we identified and characterized the full-length miiuy croaker (Miichthys miiuy) DC-SIGN (mmDC-SIGN) and L-SIGN (mmL-SIGN) genes. The sequence analysis results showed that mmDC-SIGN and mmL-SIGN have the same domains with other vertebrates except primates, and share some conserved motifs in CRD among all the vertebrates which play a crucial role in interacting with Ca(2+) and for recognizing mannose-containing motifs. Gene synteny of DC-SIGN and L-SIGN were analyzed for the first time and gene synteny of L-SIGN was conserved among the five fishes. Interestingly, one gene next to L-SIGN from gene synteny had high similarity with L-SIGN gene that was described as L-SIGN-like in fish species. While only one L-SIGN gene existed in other vertebrates, two L-SIGN in fish may be in consequence of the fish-specific genome duplication to adapt the specific environment. The evolutionary analysis showed that the ancestral lineages of L-SIGN gene in fishes experienced purifying selection and the current lineages of L-SIGN gene in fishes underwent positive selection, indicating that the ancestral lineages and current lineages of L-SIGN gene in fishes underwent different evolutionary patterns. Both mmDC-SIGN and mmL-SIGN were expressed in all tested tissues and ubiquitously up-regulated in infected liver, spleen and kidney at different sampling time points, indicating that the mmDC-SIGN and mmL-SIGN participated in the immune response to defense against bacteria infection.
树突状细胞特异性细胞间黏附分子-3抓取非整合素（DC-SIGN/CD209）和肝脏/淋巴结特异性细胞间黏附分子抓取非整合素（L-SIGN/CD299）是DC-SIGN的同源物，作为识别和清除先天性免疫系统中病原体的关键分子，是C型凝集素受体家族的重要成员。DC-SIGN和L-SIGN已成为近期研究的热点，它们在哺乳动物中均作为细胞黏附和吞噬病原体识别受体。然而，在鱼类中几乎没有关于DC-SIGN和L-SIGN结构与特性的研究，仅对斑马鱼中的DC-SIGN进行过研究。在我们的研究中，我们鉴定并表征了大黄鱼（Miichthys miiuy）的DC-SIGN（mmDC-SIGN）和L-SIGN（mmL-SIGN）基因全长。序列分析结果表明，mmDC-SIGN和mmL-SIGN与除灵长类动物外的其他脊椎动物具有相同的结构域，并且在所有脊椎动物的CRD中共享一些保守基序，这些基序在与Ca(2+)相互作用以及识别含甘露糖基序中起关键作用。首次对DC-SIGN和L-SIGN的基因共线性进行了分析，并且L-SIGN的基因共线性在这五种鱼类中是保守的。有趣的是，在基因共线性中，L-SIGN旁边的一个基因与鱼类中被描述为类L-SIGN的L-SIGN基因具有高度相似性。虽然在其他脊椎动物中仅存在一个L-SIGN基因，但鱼类中的两个L-SIGN基因可能是鱼类特异性基因组复制以适应特定环境的结果。进化分析表明，鱼类中L-SIGN基因的祖先谱系经历了纯化选择，而鱼类中L-SIGN基因的当前谱系经历了正选择，这表明鱼类中L-SIGN基因的祖先谱系和当前谱系经历了不同的进化模式。mmDC-SIGN和mmL-SIGN在所有测试组织中均有表达，并且在不同采样时间点在受感染的肝脏、脾脏和肾脏中普遍上调，这表明mmDC-SIGN和mmL-SIGN参与了对抗细菌感染的免疫反应。
