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Phosphorylation of STIM1 underlies suppression of store-operated calcium entry during mitosis

Nature Cell Biology volume 11, pages 1465–1472 (2009)Cite this article

A Corrigendum to this article was published on 01 February 2010

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Abstract

Store-operated Ca2+ entry (SOCE) and Ca2+ release-activated Ca2+ currents (Icrac) are strongly suppressed during cell division, the only known physiological situation in which Ca2+ store depletion is uncoupled from the activation of Ca2+ influx. We found that the endoplasmic reticulum (ER) Ca2+ sensor STIM1 failed to rearrange into near-plasma membrane puncta in mitotic cells, a critical step in the SOCE-activation pathway. We also found that STIM1 from mitotic cells is recognized by the phospho-specific MPM-2 antibody, suggesting that STIM1 is phosphorylated during mitosis. Removal of ten MPM-2 recognition sites by truncation at amino acid 482 abolished MPM-2 recognition of mitotic STIM1, and significantly rescued STIM1 rearrangement and SOCE response in mitosis. We identified Ser 486 and Ser 668 as mitosis-specific phosphorylation sites, and STIM1 containing mutations of these sites to alanine also significantly rescued mitotic SOCE. Therefore, phosphorylation of STIM1 at Ser 486 and Ser 668, and possibly other sites, underlies suppression of SOCE during mitosis.

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Figure 1: SOCE suppression in mitotic cells is independent of STIM1 or Orai1 expression.
Figure 2: STIM1 localization patterns are altered in mitosis.
Figure 3: STIM1 is phosphorylated during mitosis.
Figure 4: 482STOP rescues SOCE and Icrac responses in mitotic cells.
Figure 5: Phosphorylation of Ser 486 and Ser 668 contributes to SOCE suppression during mitosis.

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  • 12 January 2010

    In this letter, statements regarding the suppression of SOCE during mitosis have been altered from those initially published, Two sentences have been altered, an addtional reference added and references in the Methods renumbered. This has been corrected in both the HTML and PDF versions of the article.

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Acknowledgements

We thank J. Tucker and H. Rutledge for assistance with confocal microscopy and C. Bortner and M. Sifre for help with flow cytometry. C. Williams and D. Miller reviewed the manuscript and offered helpful suggestions. This work was supported by the Intramural Program, National Institute of Environmental Health Sciences, National Institutes of Health.

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Authors and Affiliations

  1. Department of Health and Human Services, Laboratory of Signal Transduction and National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, 27709, NC, USA

    Jeremy T. Smyth, John G. Petranka, Rebecca R. Boyles, Wayne I. DeHaven, Miwako Fukushima & James W. Putney Jr

  2. Department of Health and Human Services, Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, 27709, NC, USA

    Katina L. Johnson & Jason G. Williams

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Contributions

J.T.S. and J.G.P. performed Ca2+ measurements; J.T.S. and W.I.D. performed electrophysiology; J.T.S. performed confocal microscopy; J.T.S. and M.F. performed biochemistry; J.T.S. and R.R.B. performed molecular biology; J.G.W. and K.L.J. performed mass spectrometry. All authors performed data analysis, and J.T.S., W.I.D., J.G.W. and J.W.P. performed project planning.

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Correspondence to James W. Putney Jr.

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Smyth, J., Petranka, J., Boyles, R. et al. Phosphorylation of STIM1 underlies suppression of store-operated calcium entry during mitosis. Nat Cell Biol 11, 1465–1472 (2009). https://doi.org/10.1038/ncb1995

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