Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates  

作　　者：Manyi Yang Shaochun Yuan Shengfeng Huang Jun Li Liqun Xu Huiqing Huang Xin Tao Jian Peng Anlong Xu 

机构地区：[1]State Key Laboratory of Biocontrol, National Engineering Research Center of South China Sea Marine Biotechnology, Department of Biochemistry, College of Life Sciences, Sun Yat-Sen University, 135 W Xingang Rd, Guangzhou 510275, China

出　　处：《Cell Research》2011年第10期1410-1423,共14页细胞研究（英文版）

基　　金：This work was supported by grants from the National Basic Research Program （2007CB815800 and 2011CB946101）, the State High-Tech Development Project （2008AA092603）, International S＆T Cooperation Program from the Ministry of Science and Technology of China （2007DFA30840）, the Ministry of Education （0107）, and the National Natural Science Foundation of China （30901305, 30730089）, and the Fundamental Research Funds for the Central Universities （1 l lgzdl6）. Anlong Xu is recipient of ＂Outstanding Young Scientist Award＂ from the National Natural Science Foundation of China.

摘　　要：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-I, also known as TRIF）, while phylogenetic analy- sis 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 pro- duction of type I interferon. Thus, our study not only presents the ancestral features of vertebrate TICAM1 and TI- CAM2, 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.

关 键 词：TLR TICAM MyD88-independent pathway innate immunity evolution 

分 类 号：Q959.4[生物学—动物学] Q959.287