| First Author | Tan Y | Year | 2019 |
| Journal | Cell | Volume | 177 |
| Issue | 2 | Pages | 384-398.e11 |
| PubMed ID | 30853218 | Mgi Jnum | J:286020 |
| Mgi Id | MGI:6389922 | Doi | 10.1016/j.cell.2019.01.039 |
| Citation | Tan Y, et al. (2019) Innate Immune Signaling Organelles Display Natural and Programmable Signaling Flexibility. Cell 177(2):384-398.e11 |
| abstractText | The signaling organelles of the innate immune system consist of oligomeric protein complexes known as supramolecular organizing centers (SMOCs). Examples of SMOCs include myddosomes and inflammasomes, which respectively induce transcription-dependent and -independent inflammatory responses. The common use of oligomeric structures as signaling platforms suggests multifunctionality, but each SMOC has a singular biochemically defined function. Here, we report that the myddosome is a multifunctional organizing center. In addition to promoting inflammatory transcription factor activation, the myddosome drives the rapid induction of glycolysis. We identify the kinase TBK1 as a myddosome component that promotes glycolysis, but not nuclear factor kappaB (NF-kappaB) activation. Synthetic immunology approaches further diversified SMOC activities, as we created interferon- or necroptosis-inducing myddosomes, inflammasomes that induce interferon responses instead of pyroptosis, and a SMOC-like nanomachine that induces interferon expression in response to a chemical ligand. These discoveries demonstrate the flexibility of immune signaling organelles, which permits the design of user-defined innate immune responses. |
