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

被引：106

作者：

Sha, Haibo ^{[1
]}

Sun, Shengyi ^{[2
]}

Francisco, Adam B. ^{[3
]}

Ehrhardt, Nicole ^{[4
]}

Xue, Zhen ^{[1
]}

Liu, Lei ^{[1
]}

Lawrence, Peter ^{[1
]}

Mattijssen, Frits ^{[5
]}

Guber, Robert D. ^{[1
]}

Panhwar, Muhammad S. ^{[6
]}

Brenna, J. Thomas ^{[1
]}

Shi, Hang ^{[7
]}

Xue, Bingzhong ^{[7
]}

Kersten, Sander ^{[1
,5
]}

Bensadoun, Andre ^{[1
]}

Peterfy, Miklos ^{[4
,8
]}

Long, Qiaoming ^{[9
]}

Qi, Ling ^{[1
,2
]}

机构：

[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

[2] Cornell Univ, Grad Program Biochem Mol & Cell Biol, Ithaca, NY 14853 USA

[3] Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA

[4] Cedars Sinai Med Ctr, Med Genet Res Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA

[5] Wageningen Univ, Nutr Metab & Genom Grp, NL-6703 HD Wageningen, Netherlands

[6] Weill Cornell Med Coll Qatar, Doha, Qatar

[7] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[9] Soochow Univ, Coll Med, Lab Anim Res Ctr, Suzhou 215006, Jiangsu, Peoples R China

来源：

CELL METABOLISM | 2014年 / 20卷 / 03期

基金：

美国国家科学基金会;

关键词：

RETICULUM-ASSOCIATED-DEGRADATION; ENDOPLASMIC-RETICULUM; LIPOPROTEIN-LIPASE; CAENORHABDITIS-ELEGANS; MEMBRANE-PROTEIN; STRESS; DEFICIENCY; MATURATION; DISEASE; LIVER;

D O I：

10.1016/j.cmet.2014.06.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：458 / 470

页数：13

共 47 条

[1]

[Anonymous], INT J CELL BIOL

[2] RETRACTED: Maturation of lipoprotein lipase in the endoplasmic reticulum - Concurrent formation of functional dimers and inactive aggregates (Retracted article. See vol. 294, pg. 12565, 2019) [J].