Involvement of caveolin-1 in the Jak-Stat signaling pathway and infectious spleen and kidney necrosis virus infection in mandarin fish (Siniperca chuatsi).

Involvement of caveolin-1 in the Jak-Stat signaling pathway and infectious spleen and kidney necrosis virus infection in mandarin fish (Siniperca chuatsi).
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Caveolin-1 参与 Jak-Stat 信号通路和鳜鱼 (Siniperca chuatsi) 感染性脾肾坏死病毒感染。

DOI:
10.1016/j.molimm.2011.01.001
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发表时间:
2011-04
影响因子:
3.6
通讯作者:
He JG
He JG
中科院分区:
医学3区
文献类型:
--
作者:
Guo CJ;Yang XB;Wu YY;Yang LS;Mi S;Liu ZY;Jia KT;Huang YX;Weng SP;Yu XQ;He JG

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小窝是小窝蛋白-1的主要来源,是质膜上专门的内陷微区,在免疫系统中充当信号分子的组织中心。本研究从鳜鱼(Siniodarachuatsi)中克隆了Caveolin-1(mCav-1)基因,并研究了mCav-1在鱼类Jak-Stat信号通路和病毒感染中的作用。mCav-1的cDNA序列长707 bp,编码181个氨基酸,与哺乳动物蛋白(178个氨基酸)不同。推测的氨基酸序列与脊椎动物caveolin-1蛋白具有相似的结构,但mCav-1缺乏磷酸化位点(y14)。mCav-1的主要亚细胞位置是在小窝中,在那里蛋白质似乎具有主要功能。Real-time PCR结果显示,mCav-1支架结构域肽(mSDP)抑制了poly(I:C)诱导的Jak-Stat信号通路中的Mx、IRF-1、SOCS 1和SOCS 3基因的表达。在感染ISKNV(infectious spleen and kidney necrosis virus)的鳜鱼苗(MFF-1)细胞中,mCav-1蛋白表达在感染后12和24 h显著上调。mSDP能显著抑制ISKNV进入MFF-1细胞,且呈剂量依赖性。因此,ISKNV感染显然与mCav-1蛋白相关,并可能利用小窝相关的内吞途径。本文报道的研究结果进一步加深了我们对小窝蛋白-1在鱼类免疫系统复杂信号转导网络和虹彩病毒细胞进入机制中的功能的理解。
Caveolae, the major source of caveolin-1 protein, are specialized invaginated microdomains of the plasma membrane that act as organizing centers for signaling molecules in the immune system. In the present study, we report the cloning and characterization of caveolin-1 (mCav-1) from mandarin fish (Siniperca chuatsi) and study on the roles of mCav-1 in the fish Jak–Stat signaling pathway and in virus infection. The cDNA sequence of mCav-1 was 707 bp in size, encoding a protein of 181 amino acids, which was different from the mammalian protein (178 amino acids). The deduced amino acid sequence of mCav-1 shared similar architecture with vertebrate caveolin-1 proteins, but mCav-1 lacked a phosphorylation site (y14). The major subcellular location of mCav-1 was in the caveolae, where the protein appeared to have major functions. Real-time PCR revealed that the expression of the mandarin fish Mx, IRF-1, SOCS1, and SOCS3 genes involved in the poly(I:C)-induced Jak–Stat signaling pathway was impaired by the mCav-1 scaffolding domain peptide (mSDP). In mandarin fish fry (MFF-1) cells, the protein levels of mCav-1 were markedly up-regulated at 12 and 24 h post-infection with ISKNV (infectious spleen and kidney necrosis virus). In addition, ISKNV entry into MFF-1 cells was significantly inhibited by mSDP, and the inhibition was dose-dependent. Thus, ISKNV infection was apparently associated with mCav-1 protein and may utilize the caveolae-related endocytosis pathway. The findings reported here further our understanding of the function of caveolin-1 in the complex signal transduction network in fish immune systems and in the cellular entry mechanism of iridoviruses.
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