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Data from: Na+ influx via Orai1 inhibits intracellular ATP induced mTORC2 signaling to disrupt CD4 T cell gene expression and differentiation

Citation

Miao, Yong; Bhushan, Jaya; Dani, Adish; Vig, Monika (2017), Data from: Na+ influx via Orai1 inhibits intracellular ATP induced mTORC2 signaling to disrupt CD4 T cell gene expression and differentiation, Dryad, Dataset, https://doi.org/10.5061/dryad.202fn

Abstract

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, hydrocephalos 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 NFB 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.

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