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STIM1 dimers undergo unimolecular coupling to activate Orai1 channels

Author

Listed:
  • Yandong Zhou

    (The Pennsylvania State University College of Medicine)

  • Xizhuo Wang

    (The Pennsylvania State University College of Medicine)

  • Xianming Wang

    (The Pennsylvania State University College of Medicine)

  • Natalia A. Loktionova

    (The Pennsylvania State University College of Medicine)

  • Xiangyu Cai

    (The Pennsylvania State University College of Medicine)

  • Robert M. Nwokonko

    (The Pennsylvania State University College of Medicine)

  • Erin Vrana

    (The Pennsylvania State University College of Medicine)

  • Youjun Wang

    (College of Life Sciences, Beijing Normal University)

  • Brad S. Rothberg

    (Temple University School of Medicine)

  • Donald L. Gill

    (The Pennsylvania State University College of Medicine)

Abstract

The endoplasmic reticulum (ER) Ca2+ sensor, STIM1, becomes activated when ER-stored Ca2+ is depleted and translocates into ER–plasma membrane junctions where it tethers and activates Orai1 Ca2+ entry channels. The dimeric STIM1 protein contains a small STIM-Orai-activating region (SOAR)—the minimal sequence sufficient to activate Orai1 channels. Since SOAR itself is a dimer, we constructed SOAR concatemer–dimers and introduced mutations at F394, which is critical for Orai1 coupling and activation. The F394H mutation in both SOAR monomers completely blocks dimer function, but F394H introduced in only one of the dimeric SOAR monomers has no effect on Orai1 binding or activation. This reveals an unexpected unimolecular coupling between STIM1 and Orai1 and argues against recent evidence suggesting dimeric interaction between STIM1 and two adjacent Orai1 channel subunits. The model predicts that STIM1 dimers may be involved in crosslinking between Orai1 channels with implications for the kinetics and localization of Orai1 channel opening.

Suggested Citation

  • Yandong Zhou & Xizhuo Wang & Xianming Wang & Natalia A. Loktionova & Xiangyu Cai & Robert M. Nwokonko & Erin Vrana & Youjun Wang & Brad S. Rothberg & Donald L. Gill, 2015. "STIM1 dimers undergo unimolecular coupling to activate Orai1 channels," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9395
    DOI: 10.1038/ncomms9395
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    Cited by:

    1. Yandong Zhou & Michelle R. Jennette & Guolin Ma & Sarah A. Kazzaz & James H. Baraniak & Robert M. Nwokonko & Mallary L. Groff & Marcela Velasquez-Reynel & Yun Huang & Youjun Wang & Donald L. Gill, 2023. "An apical Phe-His pair defines the Orai1-coupling site and its occlusion within STIM1," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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