Identification of the gene that codes for the σ2 receptor

被引：228

作者：

Alon, Assaf ^{[1
]}

Schmidt, Hayden R. ^{[1
]}

Wood, Michael D. ^{[2
]}

Sahn, James J. ^{[2
]}

Martin, Stephen F. ^{[2
]}

Kruse, Andrew C. ^{[1
]}

机构：

[1] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Univ Texas Austin, Dept Chem, Austin, TX 78712 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2017年 / 114卷 / 27期

基金：

美国国家科学基金会;

关键词：

sigma-2; receptor; sigma receptors; TMEM97; cholesterol regulation; NPC1; MEMBRANE COMPONENT 1; TUMOR-CELL LINES; PGRMC1; PROTEIN; BINDING-SITE; LIGANDS; EXPRESSION; CANCER; MAC30; PROGESTERONE; DISEASE;

D O I：

10.1073/pnas.1705154114

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The sigma(2) receptor is an enigmatic protein that has attracted significant attention because of its involvement in diseases as diverse as cancer and neurological disorders. Unlike virtually all other receptors of medical interest, it has eluded molecular cloning since its discovery, and the gene that codes for the receptor remains unknown, precluding the use of modern biological methods to study its function. Using a chemical biology approach, we purified the sigma(2) receptor from tissue, revealing its identity as TMEM97, an endoplasmic reticulum-resident transmembrane protein that regulates the sterol transporter NPC1. We show that TMEM97 possesses the full suite of molecular properties that define the sigma(2) receptor, and we identify Asp29 and Asp56 as essential for ligand recognition. Cloning the sigma(2) receptor resolves a longstanding mystery and will enable therapeutic targeting of this potential drug target.

引用

页码：7160 / 7165

页数：6

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