ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1595036
Photopharmacology reveals high-specificity linkage of Ca 2+ entry at TRPC6 nanodomains to NFAT activation in mast cells
Provisionally accepted
- Medical University of Graz, Graz, Austria
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Introduction: Photopharmacology has recently emerged as a strategy for high-precision modulation of immune functions. Here we explored efficiency and specificity of interventions based on lightinduced TRPC6 activation in the RBL-2H3 mast cell model. Results: Expression of TRPC6 fusion constructs in RBL-2H3 allowed for generation of temporally well-defined, cytosolic Ca 2+ transients in response to photoisomerization of the TRPC6 actuator OptoBI-1. These Ca 2+ signals originated exclusively from Ca 2+ entry across the plasma membrane. Transient TRPC6 activation in response to UV pulses of 1s duration (3 mW/cm 2 ) just exceeded the detection threshold for monitoring of Ca 2+ signals within the TRPC6-jRGECO1a nano/microdomain. Activation of TRPC6-jRGECO1a by single, 1s UV light pulses was sufficient to trigger maximal cytosolic to nuclear translocation of NFATc1 (NFAT2) equivalent to the level generated by ionomycin (1 µM)-induced Ca 2+ entry. TRPC6 photopharmacology enabled control over NFATc1 nuclear translocation devoid of any detectable degranulation responses. Conclusion: We report here the exceptionally efficient and specific modulation of mast cell activity by TRPC6 photopharmacology.
Keywords: TRPC6, photopharmacology, Mast Cells, Basophils, Ca 2+ -transcription coupling, NFATc1 1 Introduction
Received: 18 Mar 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Krivic, Panasiuk, Pilic, Malli, Bacsa, Curcic and Groschner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Klaus Groschner, Medical University of Graz, Graz, Austria
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