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

Nat Commun. 2011 Jul 5;2:380. doi: 10.1038/ncomms1386.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorescence
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Structure
  • Multiprotein Complexes / metabolism*
  • Photoaffinity Labels / metabolism
  • Rats
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism*
  • Receptors, sigma / metabolism*

Substances

  • Ligands
  • Membrane Proteins
  • Multiprotein Complexes
  • Pgrmc1 protein, rat
  • Photoaffinity Labels
  • Receptors, Progesterone
  • Receptors, sigma
  • sigma-2 receptor

Associated data

  • PubChem-Substance/124338614
  • PubChem-Substance/124338615
  • PubChem-Substance/124338616
  • PubChem-Substance/124338617