RNA editing and its impact on GABAA receptor function

2009 ◽  
Vol 37 (6) ◽  
pp. 1399-1403 ◽  
Author(s):  
Chammiran Daniel ◽  
Marie Öhman
Keyword(s):  
Rna Editing ◽  
Surface Expression ◽  
Aminobutyric Acid ◽  
Brain Maturation ◽  
Cell Surface Expression ◽  
Receptor Subtypes ◽  
Protein Diversity ◽  
Adenosine Deaminases ◽  
Acid Type ◽  
The Impact

A-to-I (adenosine-to-inosine) RNA editing catalysed by the ADARs (adenosine deaminases that act on RNA) is a post-transcriptional event that contributes to protein diversity in metazoans. In mammalian neuronal ion channels, editing alters functionally important amino acids and creates receptor subtypes important for the development of the nervous system. The excitatory AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate glutamate receptors, as well as the inhibitory GABAA [GABA (γ-aminobutyric acid) type A] receptor, are subject to A-to-I RNA editing. Editing affects several features of the receptors, including kinetics, subunit assembly and cell-surface expression. Here, we discuss the regulation of editing during brain maturation and the impact of RNA editing on the expression of different receptor subtypes.

Dexmedetomidine Prevents Excessive γ-Aminobutyric Acid Type A Receptor Function after Anesthesia

2018 ◽  
Vol 129 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Dian-Shi Wang ◽  
Kirusanthy Kaneshwaran ◽  
Gang Lei ◽  
Fariya Mostafa ◽  
Junhui Wang ◽  
...  
Keyword(s):  
Problem Solving ◽  
Adrenergic Receptor ◽  
Hippocampal Neurons ◽  
Type A ◽  
Surface Expression ◽  
Aminobutyric Acid ◽  
Cell Surface Expression ◽  
Receptor Function ◽  
Anesthetic Drugs ◽  
Acid Type

Abstract What We Already Know about This Topic What This Article Tells Us That Is New Background Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell-surface expression and function of α5 subunit-containing γ-aminobutyric acid type A receptors, an effect that persists long after the drugs have been eliminated. Dexmedetomidine, an α2 adrenergic receptor agonist, prevents delirium in patients and reduces cognitive deficits in animals. Thus, it was postulated that dexmedetomidine prevents excessive function of α5 γ-aminobutyric acid type A receptors. Methods Injectable (etomidate) and inhaled (sevoflurane) anesthetic drugs were studied using cultured murine hippocampal neurons, cultured murine and human cortical astrocytes, and ex vivo murine hippocampal slices. γ-Aminobutyric acid type A receptor function and cell-signaling pathways were studied using electrophysiologic and biochemical methods. Memory and problem-solving behaviors were also studied. Results The etomidate-induced sustained increase in α5 γ-aminobutyric acid type A receptor cell-surface expression was reduced by dexmedetomidine (mean ± SD, etomidate: 146.4 ± 51.6% vs. etomidate + dexmedetomidine: 118.4 ± 39.1% of control, n = 8 each). Dexmedetomidine also reduced the persistent increase in tonic inhibitory current in hippocampal neurons (etomidate: 1.44 ± 0.33 pA/pF, n = 10; etomidate + dexmedetomidine: 1.01 ± 0.45 pA/pF, n = 9). Similarly, dexmedetomidine prevented a sevoflurane-induced increase in the tonic current. Dexmedetomidine stimulated astrocytes to release brain-derived neurotrophic factor, which acted as a paracrine factor to reduce excessive α5 γ-aminobutyric acid type A receptor function in neurons. Finally, dexmedetomidine attenuated memory and problem-solving deficits after anesthesia. Conclusions Dexmedetomidine prevented excessive α5 γ-aminobutyric acid type A receptor function after anesthesia. This novel α2 adrenergic receptor- and brain-derived neurotrophic factor-dependent pathway may be targeted to prevent delirium.

scholarly journals Assembly and Cell Surface Expression of Heteromeric and Homomeric -Aminobutyric Acid Type A Receptors

1996 ◽  
Vol 271 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Christopher N. Connolly ◽  
Belinda J. Krishek ◽  
Bernard J. McDonald ◽  
Trevor G. Smart ◽  
Stephen J. Moss
Keyword(s):  
Cell Surface ◽  
Type A ◽  
Surface Expression ◽  
Aminobutyric Acid ◽  
Cell Surface Expression ◽  
Acid Type

scholarly journals Phospholipase C-related but Catalytically Inactive Protein Is Required for Insulin-induced Cell Surface Expression of γ-Aminobutyric Acid Type A Receptors

2009 ◽  
Vol 285 (7) ◽  
pp. 4837-4846 ◽  
Author(s):  
Makoto Fujii ◽  
Takashi Kanematsu ◽  
Hitoshi Ishibashi ◽  
Kiyoko Fukami ◽  
Tadaomi Takenawa ◽  
...  
Keyword(s):  
Cell Surface ◽  
Phospholipase C ◽  
Type A ◽  
Surface Expression ◽  
Aminobutyric Acid ◽  
Cell Surface Expression ◽  
Acid Type ◽  
Inactive Protein

scholarly journals Endoplasmic Reticulum-associated Degradation Controls Cell Surface Expression of γ-Aminobutyric Acid, Type B Receptors

2013 ◽  
Vol 288 (48) ◽  
pp. 34897-34905 ◽  
Author(s):  
Khaled Zemoura ◽  
Marisa Schenkel ◽  
Mario A. Acuña ◽  
Gonzalo E. Yévenes ◽  
Hanns Ulrich Zeilhofer ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Surface Expression ◽  
Aminobutyric Acid ◽  
Cell Surface Expression ◽  
Type B ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Acid Type

scholarly journals HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Julie Di Cristofaro ◽  
Mathieu Pelardy ◽  
Anderson Loundou ◽  
Agnès Basire ◽  
Carine Gomez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Viral Infections ◽  
De Novo ◽  
Therapeutic Option ◽  
Univariate Analysis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hematopoietic Stem ◽  
The Impact

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12),p=0.047). HLA-E allele did not affect pathogen infection or the production ofde novoDSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

scholarly journals Functional Analysis of the Murine Cytomegalovirus Chemokine Receptor Homologue M33: Ablation of Constitutive Signaling Is Associated with an Attenuated Phenotype In Vivo

2007 ◽  
Vol 82 (4) ◽  
pp. 1884-1898 ◽  
Author(s):  
Ruth Case ◽  
Emma Sharp ◽  
Tau Benned-Jensen ◽  
Mette M. Rosenkilde ◽  
Nicholas Davis-Poynter ◽  
...  
Keyword(s):  
Cell Surface ◽  
Salivary Glands ◽  
Surface Expression ◽  
Receptor Activation ◽  
Murine Cytomegalovirus ◽  
Cell Surface Expression ◽  
Transmembrane Receptors ◽  
C Terminus ◽  
The Impact

ABSTRACT The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous studies have demonstrated that M33 is important for MCMV dissemination to or replication within the salivary glands. In this study, we probed N- and C-terminal regions of M33 as well as known 7TMR signature motifs in transmembrane (TM) II and TM III to determine the impact on cell surface expression, constitutive signaling, and in vivo phenotype. The region between amino acids R340 and A353 of the C terminus was found to be important for CREB- and NFAT-mediated signaling, although not essential for phosphatidylinositol turnover. Tagging or truncation of the N terminus of M33 resulted in loss of cell surface expression. Within TM II, an F79D mutation abolished constitutive signaling, demonstrating a role, as in other cellular and viral 7TMR, of TM II in receptor activation. In TM III, the arginine (but not the asparagine) residue of the NRY motif (the counterpart of the common DRY motif in cellular 7TMR) was found to be essential for constitutive signaling. Selected mutations incorporated into recombinant MCMV showed that disruption of constitutive signaling for a viral 7TMR homologue resulted in a reduced capacity to disseminate to or replicate in the salivary glands. In addition, HCMV UL33 was found to partially compensate for the lack of M33 in vivo, suggesting conserved biological roles of the UL33 gene family.

RNA editing by adenosine deaminases generates RNA and protein diversity

Biochimie ◽  
2002 ◽  
Vol 84 (8) ◽  
pp. 791-803 ◽  
Author(s):  
Myriam Schaub ◽  
Walter Keller
Keyword(s):  
Rna Editing ◽  
Protein Diversity ◽  
Adenosine Deaminases

scholarly journals The CD28-transmembrane domain mediates chimeric antigen receptor heterodimerization with CD28

2020 ◽  
Author(s):  
Yannick D. Muller ◽  
Duy P. Nguyen ◽  
Leonardo M.R. Ferreira ◽  
Patrick Ho ◽  
Caroline Raffin ◽  
...  
Keyword(s):  
T Cells ◽  
Chimeric Antigen Receptor ◽  
Intracellular Signaling ◽  
Transmembrane Domain ◽  
Antigen Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human T Cells ◽  
Engineered T Cells ◽  
The Impact

AbstractAnti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge (HD) and transmembrane (TMD) domains between the extracellular antigen-targeting and the intracellular signaling modalities of CARs has not been systemically studied. Here, a series of CD19-CARs differing only by their HD (CD8/CD28/IgG4) and TMD (CD8/CD28) was generated. CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation to anti-CD28 stimulation. This dimerization depended on polar amino-acids in the CD28-TMD. CD28-CAR heterodimerization was more efficient in CARs containing a CD8-HD or CD28-HD as compared to an IgG4-HD. CD28-CAR heterodimers did not respond to CD80 and CD86 stimulation but led to a significant reduction of CD28 cell-surface expression. These data unveil a new property of the CD28-TMD and suggest that TMDs can modulate CAR T-cell activities by engaging endogenous partners.Abstract Figure

Sign in / Sign up

Export Citation Format

Share Document