A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction.
A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction.
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DOI：
10.1016/j.cell.2014.01.019
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发表时间：
2014-02-13
期刊：
影响因子：
64.5
通讯作者：
Kagan JC
中科院分区：
文献类型：
--
作者：
Bonham KS;Orzalli MH;Hayashi K;Wolf AI;Glanemann C;Weninger W;Iwasaki A;Knipe DM;Kagan JC
先天免疫系统的Toll样受体（TLR）是不寻常的，因为单个家族成员位于不同的细胞器上，但大多数激活对宿主防御重要的共同信号通路。目前尚不清楚这种常见的信号通路如何从多个亚细胞位置激活。在这里，我们报告说，在响应天然激活剂的先天免疫，分选接头TIRAP调节TLR信号从质膜和内涵体。来自这两个位置的TLR信号触发了myddosome的TIRAP依赖性组装，myddosome是一种控制促炎细胞因子表达的蛋白质复合物。TIRAP的作用依赖于其磷酸肌醇结合结构域的混杂性。该结构域的不同脂质靶点将TIRAP导向不同的细胞器，使其能够调查多个隔室中是否存在活化的TLR。这些数据建立了滥交，而不是特异性，可以是一个有益的手段多样化的亚细胞位点的先天免疫信号转导。
The Toll-like receptors (TLRs) of the innate immune system are unusual in that individual family members are located on different organelles, yet most activate a common signaling pathway important for host defense. It remains unclear how this common signaling pathway can be activated from multiple subcellular locations. Here, we report that, in response to natural activators of innate immunity, the sorting adaptor TIRAP regulates TLR signaling from the plasma membrane and endosomes. TLR signaling from both locations triggers the TIRAP-dependent assembly of the myddosome, a protein complex that controls proinflammatory cytokine expression. The actions of TIRAP depend on the promiscuity of its phosphoinositide-binding domain. Different lipid targets of this domain direct TIRAP to different organelles, allowing it to survey multiple compartments for the presence of activated TLRs. These data establish how promiscuity, rather than specificity, can be a beneficial means of diversifying the subcellular sites of innate immune signal transduction.
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影响因子：
64.5
作者：
Kagan JC
通讯作者：
Kagan JC
影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
影响因子：
64.5
作者：
BAEUERLE, PA;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
64.8
作者：
Horng, T;Barton, GM;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.1073/pnas.1332608100
发表时间：
2003-06-24
影响因子：
11.1
作者：
de Boer, E;Rodriguez, P;Strouboulis, J
通讯作者：
Strouboulis, J