TY - JOUR
T1 - Photopharmacological modulation of native CRAC channels using azoboronate photoswitches
AU - Udasin, Ronald
AU - Sil, Anwesha
AU - Zomot, Elia
AU - Cohen, Hadas Achildiev
AU - Haj, Jozafina
AU - Engelmayer, Nurit
AU - Lev, Shaya
AU - Binshtok, Alexander M.
AU - Shaked, Yuval
AU - Kienzler, Michael A.
AU - Palty, Raz
N1 - Publisher Copyright:
© 2022 the Author(s).
PY - 2022/3/29
Y1 - 2022/3/29
N2 - 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.
AB - 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.
KW - CRAC channel
KW - Orai
KW - STIM
KW - azobenzene
KW - photoswitch
UR - http://www.scopus.com/inward/record.url?scp=85126873090&partnerID=8YFLogxK
U2 - 10.1073/pnas.2118160119
DO - 10.1073/pnas.2118160119
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C2 - 35312368
AN - SCOPUS:85126873090
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
M1 - e2118160119
ER -
