The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin
Abstract 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 Gαi3 signaling via an unknown mechanism. Previously, we identified the anti-autophagic activity of Tnfaip8 v...
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2017
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oai:doaj.org-article:31666f6e62154e0fb33f59d1326e8f052021-12-02T16:06:50ZThe Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin10.1038/s41598-017-06576-32045-2322https://doaj.org/article/31666f6e62154e0fb33f59d1326e8f052017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06576-3https://doaj.org/toc/2045-2322Abstract 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 Gαi3 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 Gαi3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 Å together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Gαi3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Gαi3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Gαi3 during insulin-induced anti-autophagy.Ji-Soo KimJimin ParkMi-Sun KimJi-Young HaYe-Won JangDong Hae ShinJin H. SonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Ji-Soo Kim Jimin Park Mi-Sun Kim Ji-Young Ha Ye-Won Jang Dong Hae Shin Jin H. Son The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin |
| description |
Abstract 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 Gαi3 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 Gαi3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 Å together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Gαi3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Gαi3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Gαi3 during insulin-induced anti-autophagy. |
| format |
article |
| author |
Ji-Soo Kim Jimin Park Mi-Sun Kim Ji-Young Ha Ye-Won Jang Dong Hae Shin Jin H. Son |
| author_facet |
Ji-Soo Kim Jimin Park Mi-Sun Kim Ji-Young Ha Ye-Won Jang Dong Hae Shin Jin H. Son |
| author_sort |
Ji-Soo Kim |
| title |
The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin |
| title_short |
The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin |
| title_full |
The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin |
| title_fullStr |
The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin |
| title_full_unstemmed |
The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin |
| title_sort |
tnfaip8-pe complex is a novel upstream effector in the anti-autophagic action of insulin |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/31666f6e62154e0fb33f59d1326e8f05 |
| work_keys_str_mv |
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