Reaction-diffusion model for STIM-ORAI interaction: The role of ROS and mutations

JOURNAL OF THEORETICAL BIOLOGY

卷:470

Article

Schmidt, Barbara^1,2,3,4  Alansary, Dalia³  Bogeski, Ivan^4,5  Niemeyer, Barbara A.³  Rieger, Heiko^1,2 

[1] Saarland Univ, Ctr Biophys, D-66041 Saarbrucken, Germany

[2] Saarland Univ, Dept Theoret Phys, D-66041 Saarbrucken, Germany

[3] Saarland Univ, Dept Mol Biophys, Ctr Integrat Physiol & Mol Med, D-66421 Homburg, Germany

[4] Saarland Univ, Dept Biophys, Ctr Integrat Physiol & Mol Med, D-66421 Homburg, Germany

[5] Georg August Univ, Inst Cardiovasc Physiol, Mol Physiol, Univ Med Ctr, D-37073 Gottingen, Germany

关键词: ORAI1;    STIM1;    CRAC channel;    Reaction-diffusion model;    Stoichiometry;    ROS;   

DOI  :  10.1016/j.jtbi.2019.02.010

来源: Elsevier

【 摘 要 】

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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