Photopharmacological modulation of native CRAC channels using azoboronate photoswitches

Ronald Udasin, Anwesha Sil, Elia Zomot, Hadas Achildiev Cohen, Jozafina Haj, Nurit Engelmayer, Shaya Lev, Alexander M. Binshtok, Yuval Shaked, Michael A. Kienzler*, Raz Palty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Store-operated calcium entry through calcium release–activated calcium (CRAC) channels replenishes intracellular calcium stores and plays a critical role in cellular calcium signaling. CRAC channels are activated by tightly regulated interaction between the endoplasmic reticulum (ER) calcium sensor STIM proteins and plasma membrane (PM) Orai channels. Our current understanding of the role of STIM–Orai-dependent calcium signals under physiologically relevant conditions remains limited in part due to a lack of spatiotemporally precise methods for direct manipulation of endogenous CRAC channels. Here, we report the synthesis and characterization of azoboronate light-operated CRAC channel inhibitors (LOCIs) that allow for a dynamic and fully reversible remote modulation of the function of native CRAC channels using ultraviolet (UV) and visible light. We demonstrate the use of LOCI-1 to modulate gene expression in T lymphocytes, cancer cell seeding at metastatic sites, and pain-related behavior.

Original languageAmerican English
Article numbere2118160119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number13
DOIs
StatePublished - 29 Mar 2022

Bibliographical note

Publisher Copyright:
© 2022 the Author(s).

Keywords

  • CRAC channel
  • Orai
  • STIM
  • azobenzene
  • photoswitch

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