title: The sigma-1 receptors are present in monomeric and oligomeric forms in living cells in the presence and absence of ligands.
abstract: The sigma-1 receptor (S1R) is a 223-amino-acid membrane protein that resides in the endoplasmic reticulum and the plasma membrane of some mammalian cells. The S1R is regulated by various synthetic molecules including (+)-pentazocine, cocaine and haloperidol and endogenous molecules such as sphingosine, dimethyltryptamine and dehydroepiandrosterone. Ligand-regulated protein chaperone functions linked to oxidative stress and neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and neuropathic pain have been attributed to the S1R. Several client proteins that interact with S1R have been identified including various types of ion channels and G-protein coupled receptors (GPCRs). When S1R constructs containing C-terminal monomeric GFP2 and YFP fusions were co-expressed in COS-7 cells and subjected to FRET spectrometry analysis, monomers, dimers and higher oligomeric forms of S1R were identified under non-liganded conditions. In the presence of the prototypic S1R agonist, (+)-pentazocine, however, monomers and dimers were the prevailing forms of S1R. The prototypic antagonist, haloperidol, on the other hand, favoured higher order S1R oligomers. These data, in sum, indicate that heterologously expressed S1Rs occur in vivo in COS-7 cells in multiple oligomeric forms and that S1R ligands alter these oligomeric structures. We suggest that the S1R oligomerization states may regulate its function(s).
authors.affiliation: Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Mishra
authors.affiliation: Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53211, U.S.A.
authors.forename: Timur
authors.initials: T
authors.lastname: Mavlyutov
authors.affiliation: Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Deo R
authors.initials: DR
authors.lastname: Singh
authors.affiliation: Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Biener
authors.affiliation: Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI 53211, U.S.A.
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Oliver
authors.affiliation: Department of Neuroscience, University of Wisconsin-Madison, Madison, WI 53211, U.S.A.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ruoho
authors.affiliation: Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.|Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
authors.forename: Valerică
authors.initials: V
authors.lastname: Raicu
mesh_terms: D019943:Amino Acid Substitution; D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002522:Chlorocebus aethiops; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009292:Narcotic Antagonists / Q000737:chemistry / Q000494:pharmacology; D010423:Pentazocine / Q000737:chemistry / Q000494:pharmacology; D017354:Point Mutation; D066329:Protein Aggregates / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D017480:Receptors, sigma / Q000819:agonists / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D000097605:Sigma-1 Receptor
chemical_list: D000701:Analgesics, Opioid; D006220:Haloperidol; D008024:Ligands; D008164:Luminescent Proteins; D009292:Narcotic Antagonists; D010423:Pentazocine; D066329:Protein Aggregates; D017480:Receptors, sigma; D011993:Recombinant Fusion Proteins; D000097605:Sigma-1 Receptor