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. 2014 Oct 31;18(1):pyu007.
doi: 10.1093/ijnp/pyu007.

DREADD: a chemogenetic GPCR signaling platform

Hu Zhu  1 , Bryan L Roth  2
Affiliations

DREADD: a chemogenetic GPCR signaling platform

Hu Zhu et al. Int J Neuropsychopharmacol. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Int J Neuropsychopharmacol. 2016 Apr 27;19(10):pyw031. doi: 10.1093/ijnp/pyw031. Int J Neuropsychopharmacol. 2016. PMID: 27207904 Free PMC article. No abstract available.

Abstract

Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering.

Keywords: GPCRs; GsD; chemogenetics; hM3Dq; hM4Di.

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Figures

Figure 1.
Figure 1.
Schematic diagram for the application of DREADD technology in vivo. (A) Two types of DREADD transgenic mouse models have been developed: cre-dependent and tet-dependent. DREADDs can be expressed in genetically defined cell populations after crossing with cre- or tet-off driver mouse lines. (B) Two types of DREADDs viruses were developed: cre-dependent and cre-independent. In the cre-dependent system, virus containing double-floxed inverted DREADDs are microinfused into the appropriate brain region in mice which express cell-type specific Cre drivers. DREADDs are flipped into the correct orientation and expressed after cre-mediated recombination to achieve very precise cell-type specific expression.
Figure 2.
Figure 2.
DREADDs represent a chemogenetic tool to modulate GPCR signaling in vivo. (A) Introducing two mutations in transmenbrane III and V of muscarinic receptors which create DREADDs receptors that can precisely control the Gq-, Gi-, or Gs-signaling pathways. (B) DREADDs technology has been successfully applied in β-cells, astrocytes, and a variety of neurons to control GPCR signaling in vivo. (C) DREADDs technology has a great potential to be used in drug discovery, gene therapy, and tissue engineering.
See this image and copyright information in PMC

References

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