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Calcium domain in Orai1 regulates NFAT dependent genes

Abstract: Calcium domain in Orai1 regulates genes in the immune system
Calcium is a main trigger for the immune system due to its regulation of gene expression. This signaling process controls both the proliferation of immune cells and the defense against bacteria. To mediate these cellular processes, calcium influx occurs via special pores, termed the Orai1 ion channel. Orai1 acts like a trigger that can be oscillatory or sustained opened by an immune cell. Mutations within Orai1 can result in severe immune diseases. Within this project, Dr. Rainer Schindl and his team aim to resolve which molecular structures are required for the calcium transport into immune cells and subsequent gene regulation. In preliminary experiments, we used super computers to simulate the binding of calcium with the ion channel Orai1. We hypothesize that this calcium binding domain is crucial for gene regulation. Hence the calcium binding structure will be genetically modified and compared experimentally with the function of the original Orai1 ion channel. We will record the influx of calcium into the cell, the activation of genes and the production of proteins. These methods allow to mechanistically link the molecular Orai1 structures, with calcium transport pathways and the production of proteins. The characterization of Orai1 calcium binding structure aims to provide fundamental insight into calcium transport in immune cells. Regulation of calcium influx will determine how genes are activated efficiently.

Keywords: Ca2+ abhängige Genregulation; NFAT; Orai1; speicher-abhängiger Kalziumkanal

Project Leader:: Schindl Rainer

Duration:: 01.03.2017-31.03.2021

Programme:: Einzelprojekt

Type of Research: basic research

Staff: Schindl, Rainer, Project Leader

MUG Research Units: Division of Medical Physics and Biophysics

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > STIM1 and Orai1 regulate Ca²⁺ microdoma... Biochim Biophys Acta Mol Cell Res. 2019; 1866(7):1079-1091; > Mechanistic insights into the Orai channel by mole... Semin Cell Dev Biol. 2019; 94(7):50-58; > TRPC-mediated Ca²⁺ signaling and contro... Semin Cell Dev Biol. 2019; 94:28-39; > An optically controlled probe identifies lipid-gat... Nat Chem Biol. 2018; 14(4):396-404; > Communication between N terminus and loop2 tunes O... J BIOL CHEM. 2018; 293(4): 1271-1285.