Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site. Nat Commun 2011 Jul 05;2:380
Date
07/07/2011Pubmed ID
21730960Pubmed Central ID
PMC3624020DOI
10.1038/ncomms1386Scopus ID
2-s2.0-79960099287 (requires institutional sign-in at Scopus site) 288 CitationsAbstract
The sigma-2 receptor, whose gene remains to be cloned, has been validated as a biomarker for tumour cell proliferation. Here we report the use of a novel photoaffinity probe, WC-21, to identify the sigma-2 receptor-binding site. WC-21, a sigma-2 ligand containing both a photoactive azide moiety and a fluorescein isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the membrane-bound protein was identified as PGRMC1 (progesterone receptor membrane component 1). Immunocytochemistry reveals that both PGRMC1 and SW120, a fluorescent sigma-2 receptor ligand, colocalize with molecular markers of the endoplasmic reticulum and mitochondria in HeLa cells. Overexpression and knockdown of the PGRMC1 protein results in an increase and a decrease in binding of a sigma-2 selective radioligand, respectively. The identification of the putative sigma-2 receptor-binding site as PGRMC1 should stimulate the development of unique imaging agents and cancer therapeutics that target the sigma-2 receptor/PGRMC1 complex.
Author List
Xu J, Zeng C, Chu W, Pan F, Rothfuss JM, Zhang F, Tu Z, Zhou D, Zeng D, Vangveravong S, Johnston F, Spitzer D, Chang KC, Hotchkiss RS, Hawkins WG, Wheeler KT, Mach RHMESH terms used to index this publication - Major topics in bold
AnimalsFluorescence
Gene Knockdown Techniques
HeLa Cells
Humans
Immunohistochemistry
Ligands
Membrane Proteins
Molecular Structure
Multiprotein Complexes
Photoaffinity Labels
Rats
Receptors, Progesterone
Receptors, sigma
