Troy binding to lymphotoxin-α activates NFκB mediated transcription
Troy binding to lymphotoxin-α activates NFκB mediated transcription
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DOI：
10.4161/cc.7.1.5135
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发表时间：
2008-01-01
期刊：
影响因子：
4.3
通讯作者：
Cui, Chang-Yi
中科院分区：
文献类型：
--
作者：
Hashimoto, Tsuyoshi;Schlessinger, David;Cui, Chang-Yi
Troy 是 TNFR 超家族成员，在发育中的毛囊中高度表达。然而，其在皮肤中可能的功能和配体尚不清楚。在这里，我们通过 3 种生化方法证明免疫调节细胞因子淋巴毒素-α (LT α) 是 Troy 的功能性配体：(1) 免疫沉淀分析显示 LT α（而非 LT β 或 LT α 和 LT β 的任何专性组合）与 Troy 结合。 (2) LT α 与 Troy 共转染显着上调 NF kappa B 报告基因转录，而 LT β 或 LT α 和 LT β 的组合则不然。 (3)重组LTα蛋白通过Troy以剂量依赖性方式上调NFκB活性。我们进一步发现LT α在发育中的毛囊的真皮乳头中表达，而Troy在邻近的基质区域中表达。这表明 LT α-Troy 信号传导参与毛囊发育过程中的间质-上皮相互作用。然而，在我们培育的特洛伊突变小鼠中，毛发亚型组成和形态发生了轻微改变（如果有的话）。因此，本研究表明新发现的 LT α-Troy 通路在皮肤附属器发育中具有微妙的功能，然而，它可能具有由平行 EDA 信号通路补偿的额外作用。
Troy is a TNFR superfamily member that is highly expressed in developing hair follicles. Its possible function and ligand in skin have, however, been unknown. Here we demonstrate that an immunomodulatory cytokine, lymphotoxin-alpha (LT alpha), is a functional ligand of Troy by 3 biochemical approaches: (1) Immunoprecipitation assays revealed that LT alpha, but not LT beta or any obligate combination of LT alpha and LT beta, binds to Troy. (2) Co-transfection of LT alpha with Troy sharply upregulated NF kappa B reporter transcription, whereas LT beta or a combination of LT alpha and LT beta did not. (3) Recombinant LT alpha protein upregulated NF kappa B activity through Troy in a dose-dependent manner. We further found that LT alpha is expressed in dermal papillae of developing hair follicles, whereas Troy was expressed in adjacent matrix region. This suggested involvement of LT alpha-Troy signaling in mesenchyme-epithelium interactions during hair follicle development. However, in Troy mutant mice that we generated, hair subtype composition and morphology were altered slightly if at all. The present study thus suggested a subtle function of the newly identified LT alpha-Troy pathway in skin appendage development, however, it may have an additional action compensated by a parallel EDA signaling pathway.