Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site

Jinbin Xu, Chenbo Zeng, Wenhua Chu, Fenghui Pan, Justin M. Rothfuss, Fanjie Zhang, Zhude Tu, Dong Zhou, Dexing Zeng, Suwanna Vangveravong, Fabian Johnston, Dirk Spitzer, Katherine C. Chang, Richard S. Hotchkiss, William G. Hawkins, Kenneth T. Wheeler, Robert H. MacH

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280 Scopus citations


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.

Original languageEnglish
Article number380
JournalNature communications
Issue number1
StatePublished - 2011


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