The function and pharmacology of γ-aminobutyric acid type A receptors (GABARs) are of great physiological and clinical importance and have long been thought to be determined by the channel pore-forming subunits. We discovered that Shisa7, a single-passing transmembrane protein, localizes at GABAergic inhibitory synapses and interacts with GABARs. Shisa7 controls receptor abundance at synapses and speeds up the channel deactivation kinetics. Shisa7 also potently enhances the action of diazepam, a classic benzodiazepine, on GABARs. Genetic deletion of Shisa7 selectively impairs GABAergic transmission and diminishes the effects of diazepam in mice. Our data indicate that Shisa7 regulates GABAR trafficking, function, and pharmacology and reveal a previously unknown molecular interaction that modulates benzodiazepine action in the brain.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382361 | PMC |
| http://dx.doi.org/10.1126/science.aax5719 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Methylenetetrahydrofolate reductase () C677T and A1298C polymorphisms are associated with major depressive disorder in the Saudi patients attending Erada complex for mental health and Erada services - Jeddah, Saudi Arabia.
Pharmazie
December 2024
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
: Major Depressive Disorder (MDD) is a prevalent and debilitating mental disorder that has been linked to hyperhomocysteinemia and folate deficiency. These conditions are influenced by the methylenetetrahydrofolate reductase () gene, which plays a crucial role in converting homocysteine to methionine and is essential for folate metabolism and neurotransmitter synthesis, including serotonin. : This study explored the association between and polymorphisms among Saudi MDD patients attending the Erada Complex for Mental Health and Erada Services outpatient clinic in Jeddah, Saudi Arabia.
View Article and Find Full Text PDFTargeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.
Cell Biol Toxicol
January 2025
Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China.
Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora.
View Article and Find Full Text PDFLysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.
Mol Biol Rep
January 2025
Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India.
Background: Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination.
View Article and Find Full Text PDFAlcohol drinking leads to sex-dependent differentiation of T cells.
Eur J Trauma Emerg Surg
January 2025
Department of Trauma Surgery and Orthopedics, Goethe University, University Hospital, Frankfurt, Germany.
Objective: Global per capita alcohol consumption is increasing, posing significant socioeconomic and medical challenges also due to alcohol-related traumatic injuries but also its biological effects. Trauma as a leading cause of death in young adults, is often associated with an increased risk of complications, such as sepsis and multiple organ failure, due to immunological imbalances. Regulatory T cells play a crucial role in maintaining immune homeostasis by regulating the inflammatory response.
View Article and Find Full Text PDFEffect of azithromycin combined with fluticasone propionate aerosol inhalation on immune function in children with chronic cough caused by Mycoplasma pneumoniae infection.
Eur J Pediatr
January 2025
Department of Pediatrics, Ganzhou People's Hospital, No. 16 Meiguan Avenue, Zhanggong District, Ganzhou, 341000, Jiangxi Province, China.
Unlabelled: This research aimed to describe the effect of azithromycin combined with fluticasone propionate aerosol inhalation on immune function in children with chronic cough caused by Mycoplasma pneumoniae (MP) infection. This study was a retrospective analysis in which 110 children with chronic cough caused by MP infection were divided into two groups based on different treatment methods: 58 cases in the control group treated with azithromycin dry suspension and 52 cases in the intervention group treated with azithromycin dry suspension and fluticasone propionate inhalation aerosol. Lung function, inflammatory factors, immune indicators, laboratory-related indicators, adverse reactions, and therapeutic effects were compared between the two groups.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!