| First Author | Sha H | Year | 2014 |
| Journal | Cell Metab | Volume | 20 |
| Issue | 3 | Pages | 458-70 |
| PubMed ID | 25066055 | Mgi Jnum | J:215786 |
| Mgi Id | MGI:5606246 | Doi | 10.1016/j.cmet.2014.06.015 |
| Citation | Sha H, et al. (2014) The ER-associated degradation adaptor protein Sel1L regulates LPL secretion and lipid metabolism. Cell Metab 20(3):458-70 |
| abstractText | Sel1L is an essential adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum (ER)-associated degradation (ERAD), a universal quality-control system in the cell; but its physiological role remains unclear. Here we show that mice with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity and exhibit postprandial hypertriglyceridemia. Further analyses reveal that Sel1L is indispensable for the secretion of lipoprotein lipase (LPL), independent of its role in Hrd1-mediated ERAD and ER homeostasis. Sel1L physically interacts with and stabilizes the LPL maturation complex consisting of LPL and lipase maturation factor 1 (LMF1). In the absence of Sel1L, LPL is retained in the ER and forms protein aggregates, which are degraded primarily by autophagy. The Sel1L-mediated control of LPL secretion is also seen in other LPL-expressing cell types including cardiac myocytes and macrophages. Thus, our study reports a role of Sel1L in LPL secretion and systemic lipid metabolism. |
