Nogo-B Receptor Stabilizes Niemann-Pick Type C2 Protein and Regulates Intracellular Cholesterol Trafficking

被引：75

作者：

Harrison, Kenneth D. ^{[1
,2
]}

Miao, Robert Qing ^{[1
,2
,3
,4
]}

Fernandez-Hernando, Carlos ^{[1
,2
]}

Suarez, Yajaira ^{[1
,2
]}

Davalos, Alberto ^{[1
,2
]}

Sessa, William C. ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Pharmacol & Vasc Biol, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Therapeut Program, New Haven, CT 06520 USA

[3] Med Coll Wisconsin, Childrens Res Inst, Dept Surg, Milwaukee, WI 53226 USA

[4] Med Coll Wisconsin, Childrens Res Inst, Dept Pathol, Milwaukee, WI 53226 USA

来源：

CELL METABOLISM | 2009年 / 10卷 / 03期

基金：

美国国家卫生研究院;

关键词：

LOW-DENSITY-LIPOPROTEIN; NPC1; PROTEIN; DISEASE; BINDING; IDENTIFICATION; BIOSYNTHESIS; TRANSPORT; C1; LOCALIZATION; HOMEOSTASIS;

D O I：

10.1016/j.cmet.2009.07.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Nogo-B receptor (NgBR) is a recently identified receptor for the N terminus of reticulon 4B/Nogo-B. Other than its role in binding Nogo-B, little is known about the biology of NgBR. To elucidate a basic cellular role for NgBR, we performed a yeast two-hybrid screen for interacting proteins, using the C-terminal domain as bait, and identified Niemann-Pick type C2 protein (NPC2) as an NgBR-interacting protein. NPC2 protein levels are increased in the presence of NgBR, and NgBR enhances NPC2 protein stability. NgBR localizes primarily to the endoplasmic reticulum (ER) and regulates the stability of nascent NPC2. RNAi-mediated disruption of NgBR or genetic deficiency in NgBR lead to a decrease in NPC2 levels, increased intracellular cholesterol accumulation, and a loss of sterol sensing, all hallmarks of an NPC2 mutation. These data identify NgBR as an NPC2-interacting protein and provide evidence of a role for NgBR in intracellular cholesterol trafficking.

引用

页码：208 / 218

页数：11

共 39 条

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