Dataset Information

GABA? subunits confer a bicuculline-insensitive component to GFAP+ cells of cerebellum.

ABSTRACT: GABA-A receptors mediating synaptic or extrasynaptic transmission are molecularly and functionally distinct, and glial cells are known to express a plethora of GABA-A subunits. Here we demonstrate that GFAP(+) cells of the granular layer of cerebellum express GABA? subunits during early postnatal development, thereby conferring peculiar pharmacologic characteristics to GABA responses. Electron microscopy revealed the presence of GABA? in the plasma membrane of GFAP(+) cells. In contrast, expression in the adult was restricted to Purkinje neurons and a subset of ependymal cells. Electrophysiological studies in vitro revealed that astrocytes express functional receptors with an EC50 of 52.2 ± 11.8 ?M for GABA. The evoked currents were inhibited by bicuculline (100 ?M) and TPMPA (IC50, 5.9 ± 0.6 ?M), indicating the presence of a GABA? component. Coimmunoprecipitation demonstrated protein-protein interactions between GABA?1 and GABA?1, and double immunofluorescence showed that these subunits colocalize in the plasma membrane. Three populations of GABA-A receptors in astrocytes were identified: classic GABA-A, bicuculline-insensitive GABA?, and GABA-A-GABA? hybrids. Clusters of GABA-A receptors were distributed in the perinuclear space and along the processes of GFAP(+) cells. Time-lapse microscopy showed GABA?2-GFP accumulation in clusters located in the soma and along the processes. The clusters were relatively immobile, with mean displacement of 9.4 ± 0.9 ?m and a net distance traveled of 1-2 ?m, owing mainly to directional movement or simple diffusion. Modulation of GABA? dynamics may be a novel mechanism of extrasynaptic transmission regulating GABAergic control of GFAP(+) cells during early postnatal development.

SUBMITTER: Petriz A

PROVIDER: S-EPMC4267400 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GABAρ subunits confer a bicuculline-insensitive component to GFAP+ cells of cerebellum.

Pétriz Adriana A Reyes-Haro Daniel D González-González María Alejandra MA Miledi Ricardo R Martínez-Torres Ataúlfo A

Proceedings of the National Academy of Sciences of the United States of America 20141124 49

GABA-A receptors mediating synaptic or extrasynaptic transmission are molecularly and functionally distinct, and glial cells are known to express a plethora of GABA-A subunits. Here we demonstrate that GFAP(+) cells of the granular layer of cerebellum express GABAρ subunits during early postnatal development, thereby conferring peculiar pharmacologic characteristics to GABA responses. Electron microscopy revealed the presence of GABAρ in the plasma membrane of GFAP(+) cells. In contrast, express ...[more]

PMID: 25422464

Similar Datasets

Project description:BackgroundComplement system plays an important role in innate immunity which involved in the changes tumor immune microenvironment by mediating the inflammatory response. This study aims to explore the relationship between complement component 7 (C7) polymorphisms and the risk of gastric cancer (GC).Materials and methodsAll selected SNPs of C7 were genotyped in 471 patients and 471 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional Logistic regression to analyze the relationship between each genotype and the genetic susceptibility to gastric cancer. The level of C7 expression in GC was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and detected by Enzyme Linked Immunosorbent Assay. Kaplan-Meier plotter were used to reveal C7 of prognostic value in GC. We examined SNPs associated with the expression of C7 using the GTEx database. The effect of C7 polymorphisms on the regulatory activity of C7 was detected by luciferase reporter assay.ResultsUnconditional logistic regression showed that individuals with C7 rs1376178 AA or CA genotype had a higher risk of GC with OR (95% CI) of 2.09 (1.43-3.03) and 1.88 (1.35-2.63), respectively. For C7 rs1061429 C > A polymorphism, AA genotype was associated with the elevated risk for developing gastric cancer (OR = 2.16, 95% CI [1.37-3.38]). In stratified analysis, C7 rs1376178 AA genotype increased the risk of GC among males (OR = 2.88, 95% CI [1.81-4.58]), but not among females (OR = 1.06, 95% CI [0.55-2.06]). Individuals carrying rs1061429 AA significantly increased the risk of gastric cancer among youngers (OR = 2.84, 95% CI [1.39-5.80]) and non-smokers (OR = 2.79, 95% CI [1.63-4.77]). C7 was overexpressed in gastric cancer tissues and serum of cancer patients and was significantly associated with the prognosis. C7 rs1061429 C > A variant contributed to reduced protein level of C7 (P = 0.029), but rs1376178 didn't. Luciferase reporter assay showed that rs1376178C-containing plasmid exhibited 2.86-fold higher luciferase activity than rs1376178 A-containing plasmid (P < 0.001). We also found that rs1061429A allele contributed 1.34-fold increased luciferase activity than rs1061429C allele when co-transfected with miR-591 (P = 0.0012).ConclusionsThese findings highlight the role of C7 in the development of gastric cancer.

Dataset Information

GABA? subunits confer a bicuculline-insensitive component to GFAP+ cells of cerebellum.

Publications

GABAρ subunits confer a bicuculline-insensitive component to GFAP+ cells of cerebellum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets