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A STIM2 splice variant negatively regulates store-operated calcium entry

Author

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  • Anna-Maria Miederer

    (Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48)

  • Dalia Alansary

    (Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48)

  • Gertrud Schwär

    (Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48
    Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University)

  • Po-Hsien Lee

    (Center for Bioinformatics, Saarland University, Campus E2 1, R. 315, PO Box 151150, Saarbrücken 66041, Germany)

  • Martin Jung

    (Saarland University, Building 44, Homburg 66421, Germany)

  • Volkhard Helms

    (Center for Bioinformatics, Saarland University, Campus E2 1, R. 315, PO Box 151150, Saarbrücken 66041, Germany)

  • Barbara A. Niemeyer

    (Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine (CIPMM), School of Medicine, Saarland University, Building 48)

Abstract

Cellular homeostasis relies upon precise regulation of Ca2+ concentration. Stromal interaction molecule (STIM) proteins regulate store-operated calcium entry (SOCE) by sensing Ca2+ concentration in the ER and forming oligomers to trigger Ca2+ entry through plasma membrane-localized Orai1 channels. Here we characterize a STIM2 splice variant, STIM2.1, which retains an additional exon within the region encoding the channel-activating domain. Expression of STIM2.1 is ubiquitous but its abundance relative to the more common STIM2.2 variant is dependent upon cell type and highest in naive T cells. STIM2.1 knockdown increases SOCE in naive CD4+ T cells, whereas knockdown of STIM2.2 decreases SOCE. Conversely, overexpression of STIM2.1, but not STIM2.2, decreases SOCE, indicating its inhibitory role. STIM2.1 interaction with Orai1 is impaired and prevents Orai1 activation, but STIM2.1 shows increased affinity towards calmodulin. Our results imply STIM2.1 as an additional player tuning Orai1 activation in vivo.

Suggested Citation

  • Anna-Maria Miederer & Dalia Alansary & Gertrud Schwär & Po-Hsien Lee & Martin Jung & Volkhard Helms & Barbara A. Niemeyer, 2015. "A STIM2 splice variant negatively regulates store-operated calcium entry," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7899
    DOI: 10.1038/ncomms7899
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