scholarly journals Ameliorative effect of membrane-associated estrogen receptor G protein coupled receptor 30 activation on object recognition memory in mouse models of Alzheimer's disease

2016 ◽  
Vol 131 (3) ◽  
pp. 219-222 ◽  
Author(s):  
Takashi Kubota ◽  
Hiroshi Matsumoto ◽  
Yutaka Kirino
Keyword(s):  
Alzheimer’S Disease ◽  
Estrogen Receptor ◽  
Object Recognition ◽  
Recognition Memory ◽  
G Protein ◽  
Mouse Models ◽  
G Protein Coupled Receptor ◽  
Object Recognition Memory ◽  
Ameliorative Effect ◽  
G Protein Coupled

scholarly journals Targeting the RHOA pathway improves learning and memory in Kctd13 and 16p11.2 deletion mouse models

2020 ◽  
Author(s):  
Sandra Martin Lorenzo ◽  
Valérie Nalesso ◽  
Claire Chevalier ◽  
Marie-Christine Birling ◽  
Yann Herault
Keyword(s):  
Object Recognition ◽  
Recognition Memory ◽  
Mouse Models ◽  
Copy Number Variants ◽  
Gene Copy Number ◽  
Chronic Administration ◽  
Autism Spectrum ◽  
Gene Copy ◽  
List Type ◽  
Object Recognition Memory

ABSTRACTGene copy number variants (CNV) have an important role in the appearance of neurodevelopmental disorders. Particularly, the deletion of the 16p11.2 locus is associated with autism spectrum disorder, intellectual disability, and several other features. Earlier studies highlighted the implication of Kctd13 genetic imbalance in the 16p11.2 deletion through the regulation of the RHOA pathway. Here, we target the pathway and rescue the cognitive phenotypes of the 16p11.2 deletion mouse models. We used a chronic administration of fasudil (HA1077), an inhibitor of the Rho-associated protein kinase (ROCK), in mouse models carrying a heterozygous inactivation of Kctd13, or the deletion of the entire 16p11.2 BP4-BP5 region. We focused our attention on the most robust cognitive phenotypes seen in the 16p11.2 models and we showed that a chronic fasudil treatment can restore object recognition memory in both mouse models but does not change other behavioural traits. These findings confirm KCTD13 as one target gene causing cognitive deficits in 16p11.2 deletion patients, and the pertinence of the RHOA pathway as a therapeutic path and reinforce the contribution of other gene(s) involved in cognitive defects found in the 16p11.2 CNV models.HIGHLIGHTS- Kctd13 haploinsufficiency recapitulates most of the behaviour phenotypes found in the 16p11.2 Del/+ models- Fasudil treatment restores Kctd13 and 16p11.2 Del/+ mutant phenotypes in novel location and novel object recognition memory tests- Fasudil treatment restores the RhoA pathway in Kctd13+/- and 16p11.2 Del/+ models

scholarly journals Activation of Estrogen Receptor G Protein–Coupled Receptor 30 Enhances Cholesterol Cholelithogenesis in Female Mice

Hepatology ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 2077-2089 ◽  
Author(s):  
Helen H. Wang ◽  
Ornella Bari ◽  
Christopher K. Arnatt ◽  
Min Liu ◽  
Piero Portincasa ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Female Mice ◽  
G Protein Coupled

scholarly journals Human G protein-coupled receptor 30 is N-glycosylated and N-terminal domain asparagine 44 is required for receptor structure and activity

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Ernesto Gonzalez de Valdivia ◽  
Caroline Sandén ◽  
Robin Kahn ◽  
Björn Olde ◽  
L.M. Fredrik Leeb-Lundberg
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Hek293 Cells ◽  
G Protein Coupled Receptor ◽  
Hek 293 ◽  
Receptor Structure ◽  
Terminal Domain ◽  
Endocytic Vesicles ◽  
G Protein Coupled ◽  
Structure And Activity

Abstract G protein-coupled receptor 30 (GPR30), or G protein-coupled estrogen receptor (GPER), is a G protein-coupled receptor (GPCR) that is currently attracting considerable attention in breast cancer and cardiometabolic regulation. The receptor was reported to be a novel membrane estrogen receptor mediating rapid non-genomic responses. However, questions remain about both the cognate ligand and the subcellular localization of receptor activity. Here, we used human embryonic kidney (HEK) 293 (HEK293) cells ectopically expressing N-terminally FLAG-tagged human GPR30 and three unique antibodies (Ab) specifically targetting the receptor N-terminal domain (N-domain) to investigate the role of N-glycosylation in receptor maturation and activity, the latter assayed by constitutive receptor-stimulated extracellular-regulated protein kinase (ERK) 1/2 (ERK1/2) activity. GPR30 expression was complex with receptor species spanning from approximately 40 kDa to higher molecular masses and localized in the endoplasmatic reticulum (ER), the plasma membrane (PM), and endocytic vesicles. The receptor contains three conserved asparagines, Asn25, Asn32, and Asn44, in consensus N-glycosylation motifs, all in the N-domain, and PNGase F treatment showed that at least one of them is N-glycosylated. Mutating Asn44 to isoleucine inactivated the receptor, yielding a unique receptor species at approximately 20 kDa that was recognized by Ab only in a denatured state. On the other hand, mutating Asn25 or Asn32 either individually or in combination, or truncating successively N-domain residues 1–42, had no significant effect either on receptor structure, maturation, or activity. Thus, Asn44 in the GPR30 N-domain is required for receptor structure and activity, whereas N-domain residues 1–42, including specifically Asn25 and Asn32, do not play any major structural or functional role(s).

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