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

Abstract：

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Tabor A,Weisenburger S,Banerjee A,Purkayastha N,Kaindl JM,Hübner H,Wei L,Grömer TW,Kornhuber J,Tschammer N,Birdsall NJ,Mashanov GI,Sandoghdar V,Gmeiner P

doi

10.1038/srep33233

subject

Has Abstract

pub_date

2016-09-12 00:00:00

pages

33233

issn

2045-2322

pii

srep33233

journal_volume

6

pub_type

杂志文章

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