| First Author | Kim JS | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 6248 |
| PubMed ID | 28740220 | Mgi Jnum | J:326185 |
| Mgi Id | MGI:7294457 | Doi | 10.1038/s41598-017-06576-3 |
| Citation | Kim JS, et al. (2017) The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin. Sci Rep 7(1):6248 |
| abstractText | Defective hepatic autophagy is observed in obesity and diabetes, whereas autophagy is inhibited by insulin in hepatocytes. Insulin-induced anti-autophagy is mediated by non-canonical Galphai3 signaling via an unknown mechanism. Previously, we identified the anti-autophagic activity of Tnfaip8 via activation of mammalian target of rapamycin (mTOR) in the nervous system. Here, we demonstrate that insulin temporally induces Tnfaip8, which mediates the anti-autophagic action of insulin through formation of a novel ternary complex including Tnfaip8, phosphatidylethanolamine (PE) and Galphai3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 A together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Galphai3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Galphai3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Galphai3 during insulin-induced anti-autophagy. |
