Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates
Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates
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DOI：
10.1038/cr.2011.156
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发表时间：
2011-10
期刊：
影响因子：
44.1
通讯作者：
Manyi Yang;Shaochun Yuan;Shengfeng Huang;Jun Li;Liqun Xu;Huiqing Huang;Xin Tao;Jian-xin Peng;A. Xu
中科院分区：
文献类型：
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作者：
Manyi Yang;Shaochun Yuan;Shengfeng Huang;Jun Li;Liqun Xu;Huiqing Huang;Xin Tao;Jian-xin Peng;A. Xu
MyD88非依赖通路是两条重要的TLR信号通路之一，被认为是脊椎动物的一项创新。然而，一个新的Toll/IL-1受体(TIR)适配器，命名为bbtTICAM，被发现在文昌鱼的基础上，将这一途径与无脊椎动物联系起来。BbtTICAM的蛋白质结构类似于脊椎动物TICAM1(含TIR的适配器分子-1，又称TRIF)，而基于TIR结构域的系统发育分析表明，bbtTICAM是脊椎动物TICAM1和TICAM2(含TIR的适配器分子-2，又称TRAM)最古老的同源基因。与人类TICAM 1相似，bbtTICAM通过其Rhim基序与受体相互作用蛋白(RIP)相互作用，以MyD88非依赖的方式激活NF-κB。这种激活需要bbtTICAM在内体中形成同源二聚体，它可能受到文昌鱼SARM(不育的α和含犰螂基序的蛋白)和TRAF2的负调控。但bbtTICAM不能诱导I型干扰素的产生。因此，我们的研究不仅揭示了脊椎动物TICAM1和TICAM2的祖先特征，而且揭示了MyD88非依赖于基底脊索动物的途径的进化起源，这将有助于理解脊椎动物TLR网络的发育。
The MyD88-independent pathway, one of the two crucial TLR signaling routes, is thought to be a vertebrate innovation. However, a novel Toll/interleukin-1 receptor (TIR) adaptor, designated bbtTICAM, which was identified in the basal chordate amphioxus, links this pathway to invertebrates. The protein architecture of bbtTICAM is similar to that of vertebrate TICAM1 (TIR-containing adaptor molecule-1, also known as TRIF), while phylogenetic analysis based on the TIR domain indicated that bbtTICAM is the oldest ortholog of vertebrate TICAM1 and TICAM2 (TIR-containing adaptor molecule-2, also known as TRAM). Similar to human TICAM1, bbtTICAM activates NF-κB in a MyD88-independent manner by interacting with receptor interacting protein (RIP) via its RHIM motif. Such activation requires bbtTICAM to form homodimers in endosomes, and it may be negatively regulated by amphioxus SARM (sterile α and armadillo motif-containing protein) and TRAF2. However, bbtTICAM did not induce the production of type I interferon. Thus, our study not only presents the ancestral features of vertebrate TICAM1 and TICAM2, but also reveals the evolutionary origin of the MyD88-independent pathway from basal chordates, which will aid in understanding the development of the vertebrate TLR network.