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Journal Article

NCX1 represents an ionic Na(+)sensing mechanism in macrophages

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Ebner,  Stefan
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Neubert, P., Homann, A., Wendelborn, D., Baer, A.-L., Krampert, L., Trum, M., et al. (2020). NCX1 represents an ionic Na(+)sensing mechanism in macrophages. PLOS BIOLOGY, 18(6): e3000722. doi:10.1371/journal.pbio.3000722.


Cite as: http://hdl.handle.net/21.11116/0000-0006-BA05-3
Abstract
Inflammation and infection can trigger local tissue Na(+)accumulation. This Na+-rich environment boosts proinflammatory activation of monocyte/macrophage-like cells (M phi s) and their antimicrobial activity. Enhanced Na+-driven M phi function requires the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5), which augments nitric oxide (NO) production and contributes to increased autophagy. However, the mechanism of Na(+)sensing in M phi s remained unclear. High extracellular Na(+)levels (high salt [HS]) trigger a substantial Na(+)influx and Ca(2+)loss. Here, we show that the Na+/Ca(2+)exchanger 1 (NCX1, also known as solute carrier family 8 member A1 [SLC8A1]) plays a critical role in HS-triggered Na(+)influx, concomitant Ca(2+)efflux, and subsequent augmented NFAT5 accumulation. Moreover, interfering with NCX1 activity impairs HS-boosted inflammatory signaling, infection-triggered autolysosome formation, and subsequent antibacterial activity. Taken together, this demonstrates that NCX1 is able to sense Na(+)and is required for amplifying inflammatory and antimicrobial M phi responses upon HS exposure. Manipulating NCX1 offers a new strategy to regulate M phi function.