Visualization and ligand-induced modulation of dopamine receptor dimerization at the single molecule level.

Autor:	Tabor A; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany., Weisenburger S; Max Planck Institute for the Science of Light and Department of Physics, Friedrich-Alexander University, Günther-Scharowsky-Straße 1/ Bldg. 24, 91058 Erlangen, Germany., Banerjee A; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany., Purkayastha N; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany., Kaindl JM; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany., Hübner H; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany., Wei L; Max Planck Institute for the Science of Light and Department of Physics, Friedrich-Alexander University, Günther-Scharowsky-Straße 1/ Bldg. 24, 91058 Erlangen, Germany., Grömer TW; Department of Psychiatry and Psychotherapy, Friedrich-Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany., Kornhuber J; Department of Psychiatry and Psychotherapy, Friedrich-Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany., Tschammer N; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany., Birdsall NJ; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK., Mashanov GI; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London NW7 1AA, UK., Sandoghdar V; Max Planck Institute for the Science of Light and Department of Physics, Friedrich-Alexander University, Günther-Scharowsky-Straße 1/ Bldg. 24, 91058 Erlangen, Germany., Gmeiner P; Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052 Erlangen, Germany.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2016 Sep 12; Vol. 6, pp. 33233. Date of Electronic Publication: 2016 Sep 12.
DOI:	10.1038/srep33233
Abstrakt:	G protein-coupled receptors (GPCRs), including dopamine receptors, represent a group of important pharmacological targets. An increased formation of dopamine receptor D2 homodimers has been suggested to be associated with the pathophysiology of schizophrenia. Selective labeling and ligand-induced modulation of dimerization may therefore allow the investigation of the pathophysiological role of these dimers. Using TIRF microscopy at the single molecule level, transient formation of homodimers of dopamine receptors in the membrane of stably transfected CHO cells has been observed. The equilibrium between dimers and monomers was modulated by the binding of ligands; whereas antagonists showed a ratio that was identical to that of unliganded receptors, agonist-bound D2 receptor-ligand complexes resulted in an increase in dimerization. Addition of bivalent D2 receptor ligands also resulted in a large increase in D2 receptor dimers. A physical interaction between the protomers was confirmed using high resolution cryogenic localization microscopy, with ca. 9 nm between the centers of mass.
Databáze:	MEDLINE
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