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 and Robert H. Mach ()
Additional contact information
Jinbin Xu: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Chenbo Zeng: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Wenhua Chu: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Fenghui Pan: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Justin M. Rothfuss: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Fanjie Zhang: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Zhude Tu: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Dong Zhou: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Dexing Zeng: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Suwanna Vangveravong: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
Fabian Johnston: Washington University School of Medicine
Dirk Spitzer: Washington University School of Medicine
Katherine C. Chang: Washington University School of Medicine
Richard S. Hotchkiss: Washington University School of Medicine
William G. Hawkins: Washington University School of Medicine
Kenneth T. Wheeler: Wake Forest University Health Science Center
Robert H. Mach: Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.

Nature Communications, 2011, vol. 2, issue 1, 1-7

Abstract: Abstract 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.

Date: 2011
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DOI: 10.1038/ncomms1386

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