Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 470, Issue -, Pages 64-75Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2019.02.010
Keywords
ORAI1; STIM1; CRAC channel; Reaction-diffusion model; Stoichiometry; ROS
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SFB 1027]
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Release of Ca2+ from endoplasmatic retriculum (ER) Ca2+ stores causes stromal interaction molecules (STIM) in the ER membrane and ORAL proteins in the plasma membrane (PM) to interact and form the Ca2+ release activated Ca2+ (CRAC) channels, which represent a major Ca2+ entry route in non-excitable cells and thus control various cell functions. It is experimentally possible to mutate ORAI1 proteins and therefore modify, especially block, the Ca2+ influx into the cell. On the basis of the model of Hoover and Lewis (2011), we formulate a reaction-diffusion model to quantify the STIM1-ORAI1 interaction during CRAC channel formation and analyze different ORAI1 channel stoichiometries and different ratios of STIM1 and ORAI1 in comparison with experimental data. We incorporate the inhibition of ORAI1 channels by ROS into our model and calculate its contribution to the CRAC channel amplitude. We observe a large decrease of the CRAC channel amplitude evoked by mutations of ORAI1 proteins. (C) 2019 Elsevier Ltd. All rights reserved.
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