Seipin Promotes Adipose Tissue Fat Storage through the ER Ca2+-ATPase SERCA

被引：134

作者：

Bi, Junfeng ^{[1
,2
]}

Wang, Wei ^{[1
]}

Liu, Zhonghua ^{[1
]}

Huang, Xiahe ^{[1
]}

Jiang, Qingqing ^{[1
,3
,4
]}

Liu, George ^{[3
,4
]}

Wang, Yingchun

Huang, Xun ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China

[4] Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100191, Peoples R China

来源：

CELL METABOLISM | 2014年 / 19卷 / 05期

基金：

中国国家自然科学基金;

关键词：

ENDOPLASMIC-RETICULUM STRESS; CONGENITAL LIPODYSTROPHY; INTRACELLULAR CALCIUM; CA2+; ACTIVATION; STIM1; DIFFERENTIATION; HOMEOSTASIS; METABOLISM; DEPLETION;

D O I：

10.1016/j.cmet.2014.03.028

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Adipose tissue is central to the regulation of lipid metabolism. Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), one of the most severe lipodystrophy diseases, is caused by mutation of the Seipin gene. Seipin plays an important role in adipocyte differentiation and lipid homeostasis, but its exact molecular functions are still unknown. Here, we show that Seipin physically interacts with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in both Drosophila and man. SERCA, an endoplasmic reticulum (ER) calcium pump, is solely responsible for transporting cytosolic calcium into the ER lumen. Like dSeipin, dSERCA cell-autonomously promotes lipid storage in Drosophila fat cells. dSeipin affects dSERCA activity and modulates intracellular calcium homeostasis. Adipose tissue-specific knockdown of the ER-to-cytosol calcium release channel ryanodine receptor (RyR) partially restores fat storage in dSeipin mutants. Our results reveal that Seipin promotes adipose tissue fat storage by regulating intracellular calcium homeostasis.

引用

页码：861 / 871

页数：11

共 48 条

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