title: Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site.
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.
authors: Division of Radiological Sciences, Department of Radiology, Mail Box 8225, Washington University School of Medicine, 510 S. Kingshighway Boulevard, St Louis, Missouri 63110, USA.
authors: Jinbin
authors: J
authors: Xu
authors: Chenbo
authors: C
authors: Zeng
authors: Wenhua
authors: W
authors: Chu
authors: Fenghui
authors: F
authors: Pan
authors: Justin M
authors: JM
authors: Rothfuss
authors: Fanjie
authors: F
authors: Zhang
authors: Zhude
authors: Z
authors: Tu
authors: Dong
authors: D
authors: Zhou
authors: Dexing
authors: D
authors: Zeng
authors: Suwanna
authors: S
authors: Vangveravong
authors: Fabian
authors: F
authors: Johnston
authors: Dirk
authors: D
authors: Spitzer
authors: Katherine C
authors: KC
authors: Chang
authors: Richard S
authors: RS
authors: Hotchkiss
authors: William G
authors: WG
authors: Hawkins
authors: Kenneth T
authors: KT
authors: Wheeler
authors: Robert H
authors: RH
authors: Mach
mesh_terms: D000818:Animals; D005453:Fluorescence; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000378:metabolism*; D019920:Photoaffinity Labels / Q000378:metabolism; D051381:Rats; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D046912:Multiprotein Complexes; C486424:Pgrmc1 protein, rat; D019920:Photoaffinity Labels; D011980:Receptors, Progesterone; D017480:Receptors, sigma; C106107:sigma-2 receptor