scholarly journals Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Enrica Bianchi ◽  
Yi Sun ◽  
Alexandra Almansa-Ordonez ◽  
Michael Woods ◽  
David Goulding ◽  
...  
Keyword(s):  
Fluid Flow ◽  
G Protein ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Cumulus Cells ◽  
First Trimester ◽  
G Protein Coupled Receptor ◽  
Embryo Transport ◽  
Oviductal Fluid ◽  
G Protein Coupled

AbstractDysfunction of embryo transport causes ectopic pregnancy which affects approximately 2% of conceptions in the US and Europe, and is the most common cause of pregnancy-related death in the first trimester. Embryo transit involves a valve-like tubal-locking phenomenon that temporarily arrests oocytes at the ampullary-isthmic junction (AIJ) where fertilisation occurs, but the mechanisms involved are unknown. Here we show that female mice lacking the orphan adhesion G-protein coupled receptor Adgrd1 are sterile because they do not relieve the AIJ restraining mechanism, inappropriately retaining embryos within the oviduct. Adgrd1 is expressed on the oviductal epithelium and the post-ovulatory attenuation of tubal fluid flow is dysregulated in Adgrd1-deficient mice. Using a large-scale extracellular protein interaction screen, we identified Plxdc2 as an activating ligand for Adgrd1 displayed on cumulus cells. Our findings demonstrate that regulating oviductal fluid flow by Adgrd1 controls embryo transit and we present a model where embryo arrest at the AIJ is due to the balance of abovarial ciliary action and the force of adovarial tubal fluid flow, and in wild-type oviducts, fluid flow is gradually attenuated through Adgrd1 activation to enable embryo release. Our findings provide important insights into the molecular mechanisms involved in embryo transport in mice.

Molecular mechanisms of G protein-coupled receptor desensitization and resensitization

Life Sciences ◽  
1998 ◽  
Vol 62 (17-18) ◽  
pp. 1561-1565 ◽  
Author(s):  
Stephen S.G. Ferguson ◽  
Jie Zhang ◽  
Larry S. Barakt ◽  
Marc G. Caron
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Receptor Desensitization ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

2009 ◽  
Vol 106 (29) ◽  
pp. 11925-11930 ◽  
Author(s):  
B. L. Cook ◽  
D. Steuerwald ◽  
L. Kaiser ◽  
J. Graveland-Bikker ◽  
M. Vanberghem ◽  
...  
Keyword(s):  
G Protein ◽  
Olfactory Receptor ◽  
Large Scale ◽  
Scale Production ◽  
G Protein Coupled Receptor ◽  
Large Scale Production ◽  
G Protein Coupled

scholarly journals Molecular mechanisms of G protein-coupled receptor signaling in the modulation of anxiety and conditioned fear

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S483
Author(s):  
Meejung Ko ◽  
Terrance Chiang ◽  
Arbaaz Mukadam ◽  
Grace Mulia ◽  
Julia Chester ◽  
...  
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Conditioned Fear ◽  
Receptor Signaling ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema

Hypertension ◽  
2020 ◽  
Vol 76 (5) ◽  
pp. 1625-1636 ◽  
Author(s):  
Jessica Gambardella ◽  
Daniela Sorriento ◽  
Maria Bova ◽  
Mariarosaria Rusciano ◽  
Stefania Loffredo ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
G Protein ◽  
Molecular Mechanisms ◽  
No Production ◽  
Receptor Kinase ◽  
Severe Phenotype ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Excessive BK (bradykinin) stimulation is responsible for the exaggerated permeabilization of the endothelium in angioedema. However, the molecular mechanisms underlying these responses have not been investigated. BK receptors are Gq-protein-coupled receptors phosphorylated by GRK2 (G protein-coupled receptor kinase 2) with a hitherto unknown biological and pathophysiological significance. In the present study, we sought to identify the functional role of GRK2 in angioedema through the regulation of BK signaling. We found that the accumulation of cytosolic Ca 2+ in endothelial cells induced by BK was sensitive to GRK2 activity, as it was significantly augmented by inhibiting the kinase. Accordingly, permeabilization and NO production induced by BK were enhanced, as well. In vivo, mice with reduced GRK2 levels in the endothelium (Tie2-CRE/GRK2 fl+/fl − ) exhibited an increased response to BK in terms of vascular permeability and extravasation. Finally, patients with reduced GRK2 levels displayed a severe phenotype of angioedema. Taken together, these findings establish GRK2 as a novel pivotal regulator of BK signaling with an essential role in the pathophysiology of vascular permeability and angioedema.

scholarly journals Regulation of ERRα Gene Expression by Estrogen Receptor Agonists and Antagonists in SKBR3 Breast Cancer Cells: Differential Molecular Mechanisms Mediated by G Protein-Coupled Receptor GPR30/GPER-1

2010 ◽  
Vol 24 (5) ◽  
pp. 969-980 ◽  
Author(s):  
Yin Li ◽  
Lutz Birnbaumer ◽  
Christina T. Teng
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
G Protein ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
G Protein Coupled Receptor ◽  
Ici 182,780 ◽  
G Protein Coupled

Abstract In selected tissues and cell lines, 17β-estradiol (E2) regulates the expression of estrogen-related receptor α (ERRα), a member of the orphan nuclear receptor family. This effect is thought to be mediated by the estrogen receptor α (ERα). However in the ERα- and ERβ-negative SKBR3 breast cancer cell line, physiological levels of E2 also stimulate ERRα expression. Here, we explored the molecular mechanism that mediates estrogen action in ER-negative breast cancer cells. We observed that E2, the ERα agonist, as well as the ERα antagonists ICI 182,780 and tamoxifen (TAM), a selective ER modulator, stimulate the transcriptional activity of the ERRα gene and increase the production of ERRα protein in SKBR3 cells. Moreover, the ERRα downstream target genes expression and cellular proliferation are also increased. We show further that the G protein-coupled receptor GPR30/GPER-1 (GPER-1) mediates these effects. The GPER-1 specific ligand G-1 mimics the actions of E2, ICI 182,780, and TAM on ERRα expression, and changing the levels of GPER-1 mRNA by overexpression or small interfering RNA knockdown affected the expression of ERRα accordingly. Utilizing inhibitors, we delineate a different downstream pathway for ER agonist and ER antagonist-triggered signaling through GPER-1. We also find differential histone acetylation and transcription factor recruitment at distinct nucleosomes of the ERRα promoter, depending on whether the cells are activated with E2 or with ER antagonists. These findings provide insight into the molecular mechanisms of GPER-1/ERRα-mediated signaling and may be relevant to what happens in breast cancer cells escaping inhibitory control by TAM.

scholarly journals Automated large-scale purification of a G protein-coupled receptor for neurotensin

FEBS Letters ◽  
2004 ◽  
Vol 564 (3) ◽  
pp. 289-293 ◽  
Author(s):  
Jim F White ◽  
Loc B Trinh ◽  
Joseph Shiloach ◽  
Reinhard Grisshammer
Keyword(s):  
G Protein ◽  
Large Scale ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled
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