Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China.
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Dev Comp Immunol. 2021 Mar;116:103905. doi: 10.1016/j.dci.2020.103905. Epub 2020 Oct 22.
Chemokines are a large family of soluble peptides guiding cell migration in development and immune defense. They interact with chemokine receptors and are essential for the coordination of cell migration in diverse physiological processes. The CXC subfamily is one of the largest groups in the chemokine family and consists of multiple members. In this study, we identified homologues of three chemokine ligands (CXCL8, CXCL_F5 and CXCL12) and two CXC receptor like molecules (CXCR_L1 and CXCR_L2) in lamprey. Sequence analysis revealed that they share the same genomic organization with their counterparts in jawed vertebrates but synteny was not conserved. Lamprey CXCL8 and CXCL12 have four conserved cysteine residues whilst the CXCL_F5 has two additional cysteine residues. In addition, CXCL_F5 is evolutionarily related to the fish specific CXC chemokine groups previously identified and contains multiple cationic aa residues in the extended C- terminal region. The two CXCRs possess seven transmembrane domains and conserved structural elements for receptor activation and signaling, including the DRYXXI(V)Y motif in TM2, the disulphide bond connecting ECL2 and TM3, the WXP motif in TM6 and NPXXY motif in TM7. The identified CXC chemokines and receptors were constitutively expressed in tissues including the liver, kidney, intestine, heart, gills, supraneural body and primary leukocytes, but exhibited distinct expression patterns. Relatively high expression was detected in the gills for CXCL8, CXCL_F5 and CXCR_L1 and in the supraneural body for CXCL12 and CXCR_L2. All the genes except CXCL12 were upregulated by stimulation with LPS, pokeweed and bacterial infection, and the CXCL8 and CXCL_F5 was induced by poly (I:C). Functional analysis showed that the CXCL8 and CXCL_F5 specifically interacted with CXCR_L1 and CXCR_L2, respectively. Our results demonstrate that the CXC chemokine system had diversified in jawless fish.
趋化因子是一大类可溶性肽，在发育和免疫防御中引导细胞迁移。它们与趋化因子受体相互作用，对于协调多种生理过程中的细胞迁移至关重要。CXC 亚家族是趋化因子家族中最大的家族之一，由多个成员组成。在这项研究中，我们在七鳃鳗中鉴定了三种趋化因子配体（CXCL8、CXCL_F5 和 CXCL12）和两种 CXC 受体样分子（CXCR_L1 和 CXCR_L2）的同源物。序列分析表明，它们与有颌脊椎动物的对应物具有相同的基因组组织，但同线性没有保守。七鳃鳗 CXCL8 和 CXCL12 具有四个保守的半胱氨酸残基，而 CXCL_F5 具有另外两个半胱氨酸残基。此外，CXCL_F5 与以前鉴定的鱼类特异性 CXC 趋化因子群进化相关，并且在扩展的 C 末端区域中含有多个阳离子 aa 残基。这两个 CXCR 具有七个跨膜结构域和受体激活和信号传导的保守结构元件，包括 TM2 中的 DRYXXI(V)Y 基序、连接 ECL2 和 TM3 的二硫键、TM6 中的 WXP 基序和 TM7 中的 NPXXY 基序。鉴定的 CXC 趋化因子和受体在包括肝脏、肾脏、肠道、心脏、鳃、神经上体和原代白细胞在内的组织中持续表达，但表现出不同的表达模式。CXCL8、CXCL_F5 和 CXCR_L1 在鳃中的表达相对较高，而 CXCL12 和 CXCR_L2 在神经上体中的表达较高。除了 CXCL12 之外，所有基因都被 LPS、美洲商陆和细菌感染刺激上调，而 CXCL8 和 CXCL_F5 则被 poly（I:C）诱导。功能分析表明，CXCL8 和 CXCL_F5 分别与 CXCR_L1 和 CXCR_L2 特异性相互作用。我们的结果表明，CXC 趋化因子系统在无颌鱼类中已经多样化。
