Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Maltan, L; Weiß, S; Najjar, H; Leopold, M; Lindinger, S; Höglinger, C; Höbarth, L; Sallinger, M; Grabmayr, H; Berlansky, S; Krivic, D; Hopl, V; Blaimschein, A; Fahrner, M; Frischauf, I; Tiffner, A; Derler, I.
Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1.
Nat Commun. 2023; 14(1): 1286 Doi: 10.1038/s41467-023-36458-4 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz: Krivic Denis
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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.
Find related publications in this database (using NLM MeSH Indexing): Animals - administration & dosage; Humans - administration & dosage; Calcium Release Activated Calcium Channels - metabolism; Calcium Channels - metabolism; ORAI1 Protein - genetics, metabolism; Membrane Proteins - metabolism; Cell Membrane - metabolism; Stromal Interaction Molecule 1 - genetics, metabolism; Calcium - metabolism; Calcium Signaling - physiology; Mammals - metabolism; Neoplasm Proteins - metabolism