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Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1

Author

Listed:
  • Lena Maltan

    (Johannes Kepler University Linz)

  • Sarah Weiß

    (Johannes Kepler University Linz)

  • Hadil Najjar

    (Johannes Kepler University Linz)

  • Melanie Leopold

    (Johannes Kepler University Linz)

  • Sonja Lindinger

    (Johannes Kepler University Linz)

  • Carmen Höglinger

    (Johannes Kepler University Linz)

  • Lorenz Höbarth

    (Johannes Kepler University Linz)

  • Matthias Sallinger

    (Johannes Kepler University Linz)

  • Herwig Grabmayr

    (Johannes Kepler University Linz)

  • Sascha Berlansky

    (Johannes Kepler University Linz)

  • Denis Krivic

    (Medical University of Graz)

  • Valentina Hopl

    (Johannes Kepler University Linz)

  • Anna Blaimschein

    (Johannes Kepler University Linz)

  • Marc Fahrner

    (Johannes Kepler University Linz)

  • Irene Frischauf

    (Johannes Kepler University Linz)

  • Adéla Tiffner

    (Johannes Kepler University Linz)

  • Isabella Derler

    (Johannes Kepler University Linz)

Abstract

Ca2+ release-activated Ca2+ (CRAC) channels, indispensable for the immune system and various other human body functions, consist of two transmembrane (TM) proteins, the Ca2+-sensor STIM1 in the ER membrane and the Ca2+ ion channel Orai1 in the plasma membrane. Here we employ genetic code expansion in mammalian cell lines to incorporate the photocrosslinking unnatural amino acids (UAA), p-benzoyl-L-phenylalanine (Bpa) and p-azido-L-phenylalanine (Azi), into the Orai1 TM domains at different sites. Characterization of the respective UAA-containing Orai1 mutants using Ca2+ imaging and electrophysiology reveal that exposure to UV light triggers a range of effects depending on the UAA and its site of incorporation. In particular, photoactivation at A137 using Bpa in Orai1 activates Ca2+ currents that best match the biophysical properties of CRAC channels and are capable of triggering downstream signaling pathways such as nuclear factor of activated T-cells (NFAT) translocation into the nucleus without the need for the physiological activator STIM1.

Suggested Citation

  • Lena Maltan & Sarah Weiß & Hadil Najjar & Melanie Leopold & Sonja Lindinger & Carmen Höglinger & Lorenz Höbarth & Matthias Sallinger & Herwig Grabmayr & Sascha Berlansky & Denis Krivic & Valentina Hop, 2023. "Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36458-4
    DOI: 10.1038/s41467-023-36458-4
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    References listed on IDEAS

    as
    1. Beth A. McNally & Agila Somasundaram & Megumi Yamashita & Murali Prakriya, 2012. "Gated regulation of CRAC channel ion selectivity by STIM1," Nature, Nature, vol. 482(7384), pages 241-245, February.
    2. Megumi Yamashita & Priscilla S.-W. Yeung & Christopher E. Ing & Beth A. McNally & Régis Pomès & Murali Prakriya, 2017. "STIM1 activates CRAC channels through rotation of the pore helix to open a hydrophobic gate," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    3. Guolin Ma & Lian He & Shuzhong Liu & Jiansheng Xie & Zixian Huang & Ji Jing & Yi-Tsang Lee & Rui Wang & Hesheng Luo & Weidong Han & Yun Huang & Yubin Zhou, 2020. "Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    4. Shenyuan L. Zhang & Ying Yu & Jack Roos & J. Ashot Kozak & Thomas J. Deerinck & Mark H. Ellisman & Kenneth A. Stauderman & Michael D. Cahalan, 2005. "STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane," Nature, Nature, vol. 437(7060), pages 902-905, October.
    5. Stefan Feske & Yousang Gwack & Murali Prakriya & Sonal Srikanth & Sven-Holger Puppel & Bogdan Tanasa & Patrick G. Hogan & Richard S. Lewis & Mark Daly & Anjana Rao, 2006. "A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function," Nature, Nature, vol. 441(7090), pages 179-185, May.
    6. Yandong Zhou & Xiangyu Cai & Natalia A. Loktionova & Xianming Wang & Robert M. Nwokonko & Xizhuo Wang & Youjun Wang & Brad S. Rothberg & Mohamed Trebak & Donald L. Gill, 2016. "The STIM1-binding site nexus remotely controls Orai1 channel gating," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
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