T cell effector functions require sustained calcium influx. However, the signaling and phenotypic consequences of non-specific sodium permeation via calcium channels remain unknown. α-SNAP is a crucial component of Orai1 channels, and its depletion disrupts the functional assembly of Orai1 multimers. Here we show that α-SNAP hypomorph, hydrocephalus with hopping gait, Napahyh/hyh mice harbor significant defects in CD4 T cell gene expression and Foxp3 regulatory T cell (Treg) differentiation. Mechanistically, TCR stimulation induced rapid sodium influx in Napahyh/hyh CD4 T cells, which reduced intracellular ATP, [ATP]i. Depletion of [ATP]i inhibited mTORC2 dependent NFκB activation in Napahyh/hyh cells but ablation of Orai1 restored it. Remarkably, TCR stimulation in the presence of monensin phenocopied the defects in Napahyh/hyh signaling and Treg differentiation, but not IL-2 expression. Thus, non-specific sodium influx via bonafide calcium channels disrupts unexpected signaling nodes and may provide mechanistic insights into some divergent phenotypes associated with Orai1 function.
Pubmed ID: 28492364 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsCollection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsAn Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsSoftware designed for single or multi-wavelength intracellular ion measurements. It provides simultaneous display of raw data, ratio image, graphs of intensities, ratios, ion concentrations, and a non-ratiometric image such as a brightfield or phase-contrast image. Two different ratiometric indicators can be imaged and measured simultaneously to provide greater insight to ion exchange and intracellular function regardless of dye loading concentrations, conditions, or emission intensities.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on March 17, 2022. An integrated software suite for functional analysis of experimental data. The scope of data types includes microarray and SAGE gene expression, SNPs and CGH arrays, proteomics, metabolomics, pathway analysis, Y2H and other custom interactions. MetaCore is based on a proprietary manually curated database of human protein-protein, protein-DNA and protein compound interactions, metabolic and signaling pathways and the effects of bioactive molecules in gene expression.
View all literature mentionsCommercially available software for visualization and analysis of next generation sequencing data. Used for viewing, exploring, and sharing of NGS analysis results. Complete toolkit for genomics, transcriptomics, epigenomics, and metagenomics in one program.
View all literature mentionsSoftware application for data analysis and graphing. Origin contains a variety of different graph types, including statistical plots, 2D and 3D vector graphs, and counter graphs. More advance version is OriginPro which offers advanced analysis tools and Apps for Peak Fitting, Surface Fitting, Statistics and Signal Processing.
View all literature mentionsAllele Detail: Spontaneous This is a legacy resource.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentions