The ER-Associated Degradation Adaptor Protein Sel1L Regulates LPL Secretion and Lipid Metabolism

Autor:	Robert D. Guber, Haibo Sha, Qiaoming Long, J. Thomas Brenna, Adam B. Francisco, Lei Liu, André Bensadoun, Peter Lawrence, Ling Qi, Muhammad Siyab Panhwar, Nicole Ehrhardt, Frits Mattijssen, Bingzhong Xue, Sander Kersten, Hang Shi, Zhen Xue, Shengyi Sun, Miklós Péterfy
Rok vydání:	2014
Předmět:	Male Physiology membrane-protein Voeding Metabolisme en Genomica stress Mice 0302 clinical medicine Adipocytes Cells Cultured 0303 health sciences Lipoprotein lipase biology digestive oral and skin physiology Intracellular Signaling Peptides and Proteins Signal transducing adaptor protein deficiency Endoplasmic Reticulum-Associated Degradation Metabolism and Genomics Ubiquitin ligase Metabolisme en Genomica 030220 oncology & carcinogenesis Nutrition Metabolism and Genomics Female lipids (amino acids peptides and proteins) reticulum-associated-degradation medicine.medical_specialty Endoplasmic-reticulum-associated protein degradation liver Diet High-Fat Article Protein Aggregates 03 medical and health sciences Voeding Internal medicine medicine Animals Secretion Obesity Molecular Biology Nutrition VLAG 030304 developmental biology disease maturation Endoplasmic reticulum Autophagy endoplasmic-reticulum Membrane Proteins Proteins nutritional and metabolic diseases Lipid metabolism Cell Biology Lipid Metabolism Mice Inbred C57BL caenorhabditis-elegans Lipoprotein Lipase Endocrinology lipoprotein-lipase Hyperglycemia biology.protein Protein Multimerization Gene Deletion
Zdroj:	Cell Metabolism 20 (2014) 3 Cell Metabolism, 20(3), 458-470
ISSN:	1550-4131
DOI:	10.1016/j.cmet.2014.06.015
Popis:	SummarySel1L 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.
Databáze:	OpenAIRE
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