Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):7160-7165. doi: 10.1073/pnas.1705154114. Epub 2017 May 30.

Identification of the gene that codes for the σ2 receptor.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
2
Department of Chemistry, The University of Texas at Austin, Austin, TX 78712.
3
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; andrew_kruse@hms.harvard.edu.

Abstract

The σ2 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 σ2 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 σ2 receptor, and we identify Asp29 and Asp56 as essential for ligand recognition. Cloning the σ2 receptor resolves a longstanding mystery and will enable therapeutic targeting of this potential drug target.

KEYWORDS:

NPC1; TMEM97; cholesterol regulation; sigma receptors; sigma-2 receptor

PMID:
28559337
PMCID:
PMC5502638
DOI:
10.1073/pnas.1705154114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center