scholarly journals Engineering a model cell for rational tuning of GPCR signaling

2018 ◽  
Author(s):  
William M. Shaw ◽  
Hitoshi Yamauchi ◽  
Jack Mead ◽  
Glen-Oliver F. Gowers ◽  
David Öling ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Genome Engineering ◽  
Primary Method ◽  
Signal Transduction System ◽  
Minimal Set ◽  
Gpcr Signaling ◽  
Model Cell ◽  
The Relationship ◽  
G Protein Coupled ◽  
Gpcr Signal

AbstractG protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we here constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose-response. Using four different receptors, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites and hormones relevant to human health. This work enables rational tuning of cell sensing, while providing a framework to guide reprogramming of GPCR-based signaling in more complex systems.

Histamine release by free radicals: The relationship with the signal transduction system

1989 ◽  
Vol 27 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
E. Masini ◽  
E. Giannella ◽  
A. Pistelli ◽  
B. Palmerani ◽  
F. Gambassi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Free Radicals ◽  
Histamine Release ◽  
Signal Transduction System ◽  
The Relationship

scholarly journals Molecular dynamics of the histamine H3 membrane receptor reveals different mechanisms of GPCR signal transduction

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leonardo David Herrera-Zúñiga ◽  
Liliana Marisol Moreno-Vargas ◽  
Luck Ballaud ◽  
José Correa-Basurto ◽  
Diego Prada-Gracia ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Signal Transduction ◽  
Complex Behavior ◽  
Dipalmitoyl Phosphatidyl Choline ◽  
Extensive Analysis ◽  
Long Time ◽  
Dynamics Simulations ◽  
G Protein Coupled ◽  
Gpcr Signal ◽  
Histamine H3

Abstract In this work, we studied the mechanisms of classical activation and inactivation of signal transduction by the histamine H3 receptor, a 7-helix transmembrane bundle G-Protein Coupled Receptor through long-time-scale atomistic molecular dynamics simulations of the receptor embedded in a hydrated double layer of dipalmitoyl phosphatidyl choline, a zwitterionic polysaturated ordered lipid. Three systems were prepared: the apo receptor, representing the constitutively active receptor; and two holo-receptors—the receptor coupled to the antagonist/inverse agonist ciproxifan, representing the inactive state of the receptor, and the receptor coupled to the endogenous agonist histamine and representing the active state of the receptor. An extensive analysis of the simulation showed that the three states of H3R present significant structural and dynamical differences as well as a complex behavior given that the measured properties interact in multiple and interdependent ways. In addition, the simulations described an unexpected escape of histamine from the orthosteric binding site, in agreement with the experimental modest affinities and rapid off-rates of agonists.

G-protein-coupled designer receptors – new chemical-genetic tools for signal transduction research

2013 ◽  
Vol 394 (12) ◽  
pp. 1615-1622 ◽  
Author(s):  
Gerald Thiel ◽  
Anke Kaufmann ◽  
Oliver G. Rössler
Keyword(s):  
Signal Transduction ◽  
Signaling Pathway ◽  
G Protein ◽  
Membrane Receptors ◽  
Designer Drugs ◽  
Gpcr Signaling ◽  
Chemical Genetic ◽  
G Protein Coupled

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.

Delayed appearance of G-protein coupled signal transduction system in developing cerebellar Purkinje cell dendrites

1992 ◽  
Vol 15 (3) ◽  
pp. 206-212 ◽  
Author(s):  
Hiroshi Takagi ◽  
Hideyuki Takimizu ◽  
Tohru Yoshioka ◽  
Nobuyuki Suzuki ◽  
Etsuro Ito ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Purkinje Cell ◽  
G Protein ◽  
Cerebellar Purkinje Cell ◽  
Signal Transduction System ◽  
G Protein Coupled ◽  
Purkinje Cell Dendrites

scholarly journals A complex view of GPCR signal transduction: Molecular dynamics of the histamine H3 membrane receptor

2019 ◽  
Author(s):  
L. D. Herrera-Zúñiga ◽  
L. M. Moreno-Vargas ◽  
L. Ballaud ◽  
J. Correa-Basurto ◽  
D. Prada-Gracia ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Signal Transduction ◽  
Complex Behavior ◽  
Dipalmitoyl Phosphatidyl Choline ◽  
Extensive Analysis ◽  
Long Time ◽  
Dynamics Simulations ◽  
G Protein Coupled ◽  
Gpcr Signal ◽  
Histamine H3

ABSTRACTIn this work, we study the mechanisms of classical activation and inactivation of signal transduction by the histamine H3 receptor, a 7-helix transmembrane bundle G-Protein Coupled Receptor through long-time-scale molecular dynamics simulations of the receptor embedded in a hydrated double layer of dipalmitoyl phosphatidyl choline, a zwitterionic poly-saturated ordered lipid. Three systems were prepared: the apo receptor, representing the constitutively active receptor; and two holo-receptors -the receptor coupled to the antagonist/inverse agonist ciproxifan and representing the inactive state of the receptor, and the receptor coupled to the endogenous agonist histamine and representing the active state of the receptor.An extensive analysis of the simulation shows that the three states of H3R present significant structural and dynamical differences, as well as a complex behavior given that the measured properties interact in multiple and inter-dependent ways. In addition, the simulations describe an unexpected escape of histamine from the orthosteric binding site, in agreement with the experimental modest affinities and rapid off-rates of agonists.

scholarly journals Exploring the relationship between lipoprotein mislocalization and activation of the Rcs signal transduction system in Escherichia coli

Microbiology ◽  
2012 ◽  
Vol 158 (5) ◽  
pp. 1238-1248 ◽  
Author(s):  
Yasuhiro Shiba ◽  
Hiroyoshi Miyagawa ◽  
Hideki Nagahama ◽  
Kenji Matsumoto ◽  
Daitetsu Kondo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Signal Transduction ◽  
Signal Transduction System ◽  
The Relationship
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