G Protein-Coupled Receptor Trafficking in Health and Disease: Lessons Learned to Prepare for Therapeutic Mutant Rescue in Vivo

2007 ◽  
Vol 59 (3) ◽  
pp. 225-250 ◽  
Author(s):  
P. Michael Conn ◽  
Alfredo Ulloa-Aguirre ◽  
Joel Ito ◽  
Jo Ann Janovick
Keyword(s):  
G Protein ◽  
Lessons Learned ◽  
Receptor Trafficking ◽  
G Protein Coupled Receptor ◽  
Health And Disease ◽  
G Protein Coupled ◽  
Mutant Rescue

G-Protein-Coupled Receptor Trafficking: Understanding the Chemical Basis of Health and Disease

2006 ◽  
Vol 1 (10) ◽  
pp. 631-638 ◽  
Author(s):  
Alfredo Ulloa-Aguirre ◽  
Jo Ann Janovick ◽  
Alfredo Leaños Miranda ◽  
P. Michael Conn
Keyword(s):  
G Protein ◽  
Receptor Trafficking ◽  
G Protein Coupled Receptor ◽  
Chemical Basis ◽  
Health And Disease ◽  
G Protein Coupled

scholarly journals Systematic generation of in vivo G protein-coupled receptor mutants in the rat

2010 ◽  
Vol 11 (5) ◽  
pp. 326-336 ◽  
Author(s):  
R van Boxtel ◽  
B Vroling ◽  
P Toonen ◽  
I J Nijman ◽  
H van Roekel ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Hybrid Transgenic Mice Reveal In Vivo Specificity of G Protein–Coupled Receptor Kinases in the Heart

2000 ◽  
Vol 86 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Andrea D. Eckhart ◽  
Sandra J. Duncan ◽  
Raymond B. Penn ◽  
Jeffrey L. Benovic ◽  
Robert J. Lefkowitz ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Receptor Kinases ◽  
G Protein Coupled

scholarly journals Vascular Abnormalities in Mice Deficient for the G Protein-Coupled Receptor GPR4 That Functions as a pH Sensor

2006 ◽  
Vol 27 (4) ◽  
pp. 1334-1347 ◽  
Author(s):  
Li V. Yang ◽  
Caius G. Radu ◽  
Meenakshi Roy ◽  
Sunyoung Lee ◽  
Jami McLaughlin ◽  
...  
Keyword(s):  
G Protein ◽  
Mesangial Cells ◽  
Ex Vivo ◽  
Extracellular Ph ◽  
Ph Sensing ◽  
G Protein Coupled Receptor ◽  
Vascular Abnormalities ◽  
G Protein Coupled

ABSTRACT GPR4 is a G protein-coupled receptor expressed in the vasculature, lung, kidney, and other tissues. In vitro ectopic overexpression studies implicated GPR4 in sensing extracellular pH changes leading to cyclic AMP (cAMP) production. To investigate its biological roles in vivo, we generated GPR4-deficient mice by homologous recombination. Whereas GPR4-null adult mice appeared phenotypically normal, neonates showed a higher frequency of perinatal mortality. The average litter size from GPR4−/− intercrosses was ∼30% smaller than that from GPR4+/+ intercrosses on N3 and N5 C57BL/6 genetic backgrounds. A fraction of knockout embryos and neonates had spontaneous hemorrhages, dilated and tortuous subcutaneous blood vessels, and defective vascular smooth muscle cell coverage. Mesangial cells in kidney glomeruli were also significantly reduced in GPR4-null neonates. Some neonates exhibited respiratory distress with airway lining cell metaplasia. To examine whether GPR4 is functionally involved in vascular pH sensing, an ex vivo aortic ring assay was used under defined pH conditions. Compared to wild-type aortas, microvessel outgrowth from GPR4-null aortas was less inhibited by acidic extracellular pH. Treatment with an analog of cAMP, a downstream effector of GPR4, abolished microvessel outgrowth bypassing the GPR4-knockout phenotype. These results suggest that GPR4 deficiency leads to partially penetrant vascular abnormalities during development and that this receptor functions in blood vessel pH sensing.

scholarly journals Deficiency of Proton-Sensing Ovarian Cancer G Protein-Coupled Receptor 1 Attenuates Glucose-Stimulated Insulin Secretion

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4171-4180 ◽  
Author(s):  
Takashi Nakakura ◽  
Chihiro Mogi ◽  
Masayuki Tobo ◽  
Hideaki Tomura ◽  
Koichi Sato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Insulin Secretion ◽  
G Protein ◽  
Normal Glucose Tolerance ◽  
Extracellular Ph ◽  
G Protein Coupled Receptor ◽  
Glucose Stimulated Insulin Secretion ◽  
G Protein Coupled

Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown as a receptor for protons. In the present study, we aimed to know whether OGR1 plays a role in insulin secretion and, if so, the manner in which it does. To this end, we created OGR1-deficient mice and examined insulin secretion activity in vivo and in vitro. OGR1 deficiency reduced insulin secretion induced by glucose administered ip, although it was not associated with glucose intolerance in vivo. Increased insulin sensitivity and reduced plasma glucagon level may explain, in part, the unusual normal glucose tolerance. In vitro islet experiments revealed that glucose-stimulated insulin secretion was dependent on extracellular pH and sensitive to OGR1; insulin secretion at pH 7.4 to 7.0, but not 8.0, was significantly suppressed by OGR1 deficiency and inhibition of Gq/11 proteins. Insulin secretion induced by KCl and tolbutamide was also significantly inhibited, whereas that induced by several insulin secretagogues, including vasopressin, a glucagon-like peptide 1 receptor agonist, and forskolin, was not suppressed by OGR1 deficiency. The inhibition of insulin secretion was associated with the reduction of glucose-induced increase in intracellular Ca2+ concentration. In conclusion, the OGR1/Gq/11 protein pathway is activated by extracellular protons existing under the physiological extracellular pH of 7.4 and further stimulated by acidification, resulting in the enhancement of insulin secretion in response to high glucose concentrations and KCl.

The ins and outs of G protein-coupled receptor trafficking

2003 ◽  
Vol 28 (7) ◽  
pp. 369-376 ◽  
Author(s):  
Adriano Marchese ◽  
Catherine Chen ◽  
You-Me Kim ◽  
Jeffrey L. Benovic
Keyword(s):  
G Protein ◽  
Receptor Trafficking ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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