title: The specific monomer/dimer equilibrium of the corticotropin-releasing factor receptor type 1 is established in the endoplasmic reticulum.
abstract: G protein-coupled receptors (GPCRs) represent the most important drug targets. Although the smallest functional unit of a GPCR is a monomer, it became clear in the past decades that the vast majority of the receptors form dimers. Only very recently, however, data were presented that some receptors may in fact be expressed as a mixture of monomers and dimers and that the interaction of the receptor protomers is dynamic. To date, equilibrium measurements were restricted to the plasma membrane due to experimental limitations. We have addressed the question as to where this equilibrium is established for the corticotropin-releasing factor receptor type 1. By developing a novel approach to analyze single molecule fluorescence cross-correlation spectroscopy data for intracellular membrane compartments, we show that the corticotropin-releasing factor receptor type 1 has a specific monomer/dimer equilibrium that is already established in the endoplasmic reticulum (ER). It remains constant at the plasma membrane even following receptor activation. Moreover, we demonstrate for seven additional GPCRs that they are expressed in specific but substantially different monomer/dimer ratios. Although it is well known that proteins may dimerize in the ER in principle, our data show that the ER is also able to establish the specific monomer/dimer ratios of GPCRs, which sheds new light on the functions of this compartment.
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Anke
authors: A
authors: Teichmann
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Arthur
authors: A
authors: Gibert
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: André
authors: A
authors: Lampe
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Paul
authors: P
authors: Grzesik
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Claudia
authors: C
authors: Rutz
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Jens
authors: J
authors: Furkert
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Jan
authors: J
authors: Schmoranzer
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Gerd
authors: G
authors: Krause
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany wiesner@fmp-berlin.de.
authors: Burkhard
authors: B
authors: Wiesner
authors: From the Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany schuelein@fmp-berlin.de.
authors: Ralf
authors: R
authors: Schülein
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1
keywords: Confocal Microscopy; Corticotropin-releasing Factor Receptors; Endoplasmic Reticulum (ER); Fluorescence Correlation Spectroscopy (FCS); Fluorescence Cross-correlation Spectroscopy; G Protein-coupled Receptor (GPCR); Monomer/Oligomer Equilibrium; Plasma Membrane; Receptor Oligomerization