Amphioxus SARM Involved in Neural Development May Function as a Suppressor of TLR Signaling

Yuan, Shaochun; Wu, Kui; Yang, Manyi; Xu, Liqun; Huang, Ling; Liu, Huiling; Tao, Xin; Huang, Shengfeng; Xu, Anlong

doi:10.4049/jimmunol.0903675

Cited by 45 publications

(44 citation statements)

References 30 publications

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“…Con- versely, TRAF1, TRAF4 and SARM act as inhibitors in TICAM1-dependent signaling [33][34][35][36]. As amphioxus TRAF2, TRAF3, TRAF4, TRAF6, and SARM were cloned by our group in other studies [37][38][39], we investigated the relationship between these molecules and bbt-TICAM. The results showed that bbtTRAF3, bbtTRAF4, and bbtTRAF6 had no effect on the NF-κB activation mediated by bbtTICAM (Supplementary information, Figure S5A-S5C), while bbtTRAF2 and bbtSARM attenuated the activity of bbtTICAM in a dose-dependent manner ( Figure 7A and 7B).…”

Section: Bbtticam Failed To Interact With Bbttraf3 4 and 6 But Assmentioning

confidence: 99%

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

et al. 2011

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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 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.

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Section: Bbtticam Failed To Interact With Bbttraf3 4 and 6 But Assmentioning

confidence: 99%

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

et al. 2011

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“…In our previous studies of amphioxus TLRs and related signaling molecules, we provided compelling evidence for a functional intracellular TLR-NF-kB signaling cascade (25,31,32,34). Amphioxus expresses $48 TLRs and .40 TIR-containing adaptors, which suggests an expanded repertoire of adaptors and intermediate signal transducers in its TLR signaling pathways.…”

Section: Oomentioning

confidence: 99%

“…Embryo collection, section in situ hybridization, Southern blot hybridization, RT-PCR analysis, immunofluorescence imaging, transient transfection, luciferase reporter assay, and coimmunoprecipitation (co-IP) were performed as described previously (23)(24)(25). Primers for hybridization probe preparation and RT-PCR are listed in Supplemental Table I.…”

Section: Nuclear Extraction and Emsamentioning

confidence: 99%

The Archaic Roles of the Amphioxus NF-κB/IκB Complex in Innate Immune Responses

Yuan

Zhang

et al. 2013

The Journal of Immunology

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NF-κB transcription factors play important roles in immune responses and the development of the immune system. Many aspects of NF-κB signaling differ significantly among distinct species, although many similarities in signaling exist in flies and humans. Thus, to understand the functional refinement of the NF-κB cascade from invertebrates to vertebrates, the Rel and NF-κB proteins, identified as bbtRel and bbtp105, were characterized in a basal chordate amphioxus. Consistent with the sequence similarities, bbtRel was found to interact with a mammalian κB response element, to move into the nucleus when activated, and to be inhibited by the NF-κB–specific inhibitor helenalin. Similar to the other class I members, bbtp105 could be cleaved into the mature form p58. Such endoproteolysis depends on the GRR sequence and requires both protease degradation and caspase 8 cleavage. Furthermore, we found that bbtIκB and the unprocessed bbtp105 can inhibit the transcriptional activity of bbtRel, whereas bbtp58 forms homodimers or heterodimers with bbtRel to create a mature NF-κB complex. Finally, we found that the survival rate and the expression of bbtIκB and TNF-α–like genes were decreased when adult amphioxus were treated with helanalin before immune challenge, suggesting the archaic roles for NF-κB signaling in innate immune responses in a basal chordate. The presence of the NF-κB–IκB cascade in amphioxus indicates that it is a significant feature linking invertebrates to vertebrates and is refined in vertebrates through the expansion and divergence of genes involved in the cascade.

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“…To reduce microbial abundance, on the day prior to dissection, amphioxi were transferred to sea water that was filtered with a 0.45-mm filter and contained 10 mg/ml penicillin. After amphioxi were anesthetized, the amphioxus intestines were extracted, dissected into pieces, and digested for 2 h at 23˚C with 1% collagenase type II (Life Sectional in situ hybridization was performed according to the protocol described previously (34). Luciferase reporter assay, Co-IP, FIGURE 1.…”

Section: Culture Of Amphioxus Intestinal Cells and Poly(i:c) Transfecmentioning

confidence: 99%

Characterization of Amphioxus IFN Regulatory Factor Family Reveals an Archaic Signaling Framework for Innate Immune Response

Yuan

Zheng

et al. 2015

The Journal of Immunology

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The IFN regulatory factor (IRF) family encodes transcription factors that play important roles in immune defense, stress response, reproduction, development, and carcinogenesis. Although the origin of the IRF family has been dated back to multicellular organisms, invertebrate IRFs differ from vertebrate IRFs in genomic structure and gene synteny, and little is known about their functions. Through comparison of multiple amphioxus genomes, in this study we suggested that amphioxus contains nine IRF members, whose orthologs are supposed to be shared among three amphioxus species. As the orthologs to the vertebrate IRF1 and IRF4 subgroups, Branchiostoma belcheri tsingtauense (bbt)IRF1 and bbtIRF8 bind the IFN-stimulated response element (ISRE) and were upregulated when amphioxus intestinal cells were stimulated with poly(I:C). As amphioxus-specific IRFs, both bbtIRF3 and bbtIRF7 bind ISRE. When activated, they can be phosphorylated by bbtTBK1 and then translocate into nucleus for target gene transcription. As transcriptional repressors, bbtIRF2 and bbtIRF4 can inhibit the transcriptional activities of bbtIRF1, 3, 7, and 8 by competing for the binding of ISRE. Interestingly, amphioxus IRF2, IRF8, and Rel were identified as target genes of bbtIRF1, bbtIRF7, and bbtIRF3, respectively, suggesting a dynamic feedback regulation among amphioxus IRF and NF-κB. Collectively, to our knowledge we present for the first time an archaic IRF signaling framework in a basal chordate, shedding new insights into the origin and evolution of vertebrate IFN-based antiviral networks.

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Amphioxus SARM Involved in Neural Development May Function as a Suppressor of TLR Signaling

Cited by 45 publications

References 30 publications

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

The Archaic Roles of the Amphioxus NF-κB/IκB Complex in Innate Immune Responses

Characterization of Amphioxus IFN Regulatory Factor Family Reveals an Archaic Signaling Framework for Innate Immune Response

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