CALCIUM SIGNALING the Ca2+ export pump PMCA clears near-membrane Ca2+ to facilitate store-operated Ca2+ entry and NFAT activation

Christina K. Go, Robert Hooper, Matthew R. Aronson, Bryant Schultz, Taha Cangoz, Neeharika Nemani, Yi Zhang, Muniswamy Madesh, Jonathan Soboloff

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Ca2+ signals, which facilitate pluripotent changes in cell fate, reflect the balance between cation entry and export. We found that overexpression of either isoform of the Ca2+-extruding plasma membrane calcium ATPase 4 (PMCA4) pump in Jurkat T cells unexpectedly increased activation of the Ca2+-dependent transcription factor nuclear factor of activated T cells (NFAT). Coexpression of the endoplasmic reticulum–resident Ca2+ sensor stromal interaction molecule 1 (STIM1) with the PMCA4b splice variant further enhanced NFAT activity; however, coexpression with PMCA4a depressed NFAT. No PMCA4 splice variant dependence in STIM1 association was observed, whereas partner of STIM1 (POST) preferentially associated with PMCA4b over PMCA4a, which enhanced, rather than inhibited, PMCA4 function. A comparison of global and near-membrane cytosolic Ca2+ abundances during store-operated Ca2+ entry revealed that PMCA4 markedly depressed near-membrane Ca2+ concentrations, particularly when PMCA4b was coexpressed with STIM1. PMCA4b closely associated with both POST and the store-operated Ca2+ channel Orai1. Furthermore, POST knockdown increased the near-membrane Ca2+ concentration, inhibiting the global cytosolic Ca2+ increase. These observations reveal an unexpected role for POST in coupling PMCA4 to Orai1 to promote Ca2+ entry during T cell activation through Ca2+ disinhibition.

Original languageEnglish (US)
Article numbereaaw2627
JournalScience signaling
Volume12
Issue number602
DOIs
StatePublished - Oct 8 2019
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Go, C. K., Hooper, R., Aronson, M. R., Schultz, B., Cangoz, T., Nemani, N., Zhang, Y., Madesh, M., & Soboloff, J. (2019). CALCIUM SIGNALING the Ca2+ export pump PMCA clears near-membrane Ca2+ to facilitate store-operated Ca2+ entry and NFAT activation. Science signaling, 12(602), [eaaw2627]. https://doi.org/10.1126/scisignal.aaw2627