학술논문
The ER-associated degradation adaptor protein Sel1L regulates LPL secretion and lipid metabolism.
Document Type
Academic Journal
Author
Sha H; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Sun S; Graduate Program in Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA.; Francisco AB; Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.; Ehrhardt N; Department of Biomedical Sciences, Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.; Xue Z; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Liu L; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Lawrence P; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Mattijssen F; Nutrition Metabolism and Genomics Group, Wageningen University, Wageningen 6703HD, the Netherlands.; Guber RD; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Panhwar MS; Weill Cornell Medical College in Qatar, P.O. Box 24144, Education City, Doha, Qatar.; Brenna JT; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Shi H; Department of Biology, Georgia State University, Atlanta, GA 30303, USA.; Xue B; Department of Biology, Georgia State University, Atlanta, GA 30303, USA.; Kersten S; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Nutrition Metabolism and Genomics Group, Wageningen University, Wageningen 6703HD, the Netherlands.; Bensadoun A; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.; Péterfy M; Department of Biomedical Sciences, Medical Genetics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.; Long Q; Laboratory Animal Research Center, Medical College of Soochow University, Suzhou, Jiangsu 215006, China.; Qi L; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Graduate Program in Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA. Electronic address: lq35@cornell.edu.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
(Copyright © 2014 Elsevier Inc. All rights reserved.)