Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Krivić, D; Panasiuk, O; Pilic, J; Malli, R; Bacsa, B; Ćurčić, S; Groschner, K.
Photopharmacology reveals high-specificity linkage of Ca2+ entry at TRPC6 nanodomains to NFAT activation in mast cells.
Front Immunol. 2025; 16: 1595036
Doi: 10.3389/fimmu.2025.1595036
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- Autor*innen der Med Uni Graz:
- Bacsa Bernadett
- Groschner Klaus
- Malli Roland
- Panasiuk Olga
- Pilic Johannes
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- Abstract:
- 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 light-induced 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 Ca2+ transients in response to photoisomerization of the TRPC6 actuator OptoBI-1. These Ca2+ signals originated exclusively from Ca2+ entry across the plasma membrane. Transient TRPC6 activation in response to UV pulses of 1s duration (3 mW/cm2) just exceeded the detection threshold for monitoring of Ca2+ 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 Ca2+ 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Mast Cells - metabolism, immunology, radiation effects
- NFATC Transcription Factors - metabolism
- TRPC6 Cation Channel - metabolism, genetics
- Calcium - metabolism
- Animals - administration & dosage
- Calcium Signaling - radiation effects
- Ultraviolet Rays - administration & dosage
- Rats - administration & dosage
- Cell Degranulation - administration & dosage
- Cell Line - administration & dosage
- Humans - administration & dosage