Unusual Regulation of a STAT Protein by an SLC6 Family Transporter in C. elegans Epidermal Innate Immunity
Unusual Regulation of a STAT Protein by an SLC6 Family Transporter in C. elegans Epidermal Innate Immunity
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DOI：
10.1016/j.chom.2011.04.011
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发表时间：
2011-05-19
影响因子：
30.3
通讯作者：
Pujol, Nathalie
中科院分区：
文献类型：
--
作者：
Dierking, Katja;Polanowska, Jolanta;Pujol, Nathalie
秀丽隐杆线虫的角质层和表皮是抵御病原体入侵的第一道防线。在真菌病原菌锥孢锥孢霉（Drechmeria coniospora）侵入后，C.线虫通过激活至少两种途径（神经内分泌TGF-β途径和p38 MAPK途径）上调表皮中抗菌肽（AMP）的表达来响应。在这里，我们确定了钠-神经递质同向转运体SNF-12，溶质载体家族（SLC 6）的成员，作为这两个免疫信号通路所必需的。我们还确定了STAT转录因子样蛋白STA-2作为SNF-12的直接物理相互作用，并表明这两种蛋白质共同作用，以调节AMP基因在表皮中的表达。SNF-12和STA-2都在表皮中自主且特异性地作用于细胞，以控制对真菌感染的转录反应。这些发现揭示了STAT因子的非正统调节模式，并突出了先天免疫信号传导的分子可塑性。
The cuticle and epidermis of Caenorhabditis elegans provide the first line of defense against invading pathogens. Upon invasion by the fungal pathogen Drechmeria coniospora, C. elegans responds by upregulating the expression of antimicrobial peptides (AMPs) in the epidermis via activation of at least two pathways, a neuroendocrine TGF-beta pathway and a p38 MAPK pathway. Here, we identify the sodium-neurotransmitter symporter SNF-12, a member of the solute carrier family (SLC6), as being essential for both these immune signaling pathways. We also identify the STAT transcription factor-like protein STA-2 as a direct physical interactor of SNF-12 and show that the two proteins function together to regulate AMP gene expression in the epidermis. Both SNF-12 and STA-2 act cell autonomously and specifically in the epidermis to govern the transcriptional response to fungal infection. These findings reveal an unorthodox mode of regulation for a STAT factor and highlight the molecular plasticity of innate immune signaling.