G-protein-coupled designer receptors – new chemical-genetic tools for signal transduction research
-
Gerald Thiel
,
Anke Kaufmann
Abstract
G-protein-coupled receptors (GPCRs) are the largest group of plasma membrane receptors in nature and are activated by a variety of different ligands. The biological outcome of GPCR stimulation is complex, as a plethora of signaling pathways are activated upon stimulation. These complexity and diversity of GPCR signaling make it difficult to manipulate the signaling pathway of a specific GPCR by natural ligands. To reduce the complexity in experimental settings, specific pharmacological ligands that preferentially activate one signaling pathway have been developed. In addition, G-protein-coupled designer receptors that are unresponsive to endogenous ligands but can be activated by otherwise pharmacologically inert compounds have been designed. These receptors have been termed designer receptors exclusively activated by designer drugs. The lack of constitutive activity of these designer receptors allows their use for in vitro and in vivo studies of GPCR-mediated signal transduction. The analysis of recently generated transgenic mice showed that the expression of G-protein-coupled designer receptors represents a powerful chemical-genetic tool to investigate GPCR signaling and function.
We thank Libby Guethlein for the critical reading of the manuscript. The research on the expression and activity of G-protein-coupled designer receptors was funded by the ‘Zentrale Forschungskommission’ of the University of Saarland.
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Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: perspectives in molecular neurobiology
- HIGHLIGHT: PERSPECTIVES IN MOLECULAR NEUROBIOLOGY
- Role of the peroxisome proliferator-activated receptors (PPAR)-α, β/δ and γ triad in regulation of reactive oxygen species signaling in brain
- Molecular triggers of neuroinflammation in mouse models of demyelinating diseases
- Sox appeal – Sox10 attracts epigenetic and transcriptional regulators in myelinating glia
- MeCP2 phosphorylation in the brain: from transcription to behavior
- The nuclear receptor peroxisome proliferator-activated receptor-γ promotes oligodendrocyte differentiation through mechanisms involving mitochondria and oscillatory Ca2+ waves
- G-protein-coupled designer receptors – new chemical-genetic tools for signal transduction research
- Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells
- Reviews
- Eternity and functionality – rational access to physiologically relevant cell lines
- Structural and functional insights into the Spir/formin actin nucleator complex
