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- W2405842331 abstract "Calcium dynamics lie at the heart of many adaptive cellular signals and are thus tightly controlled. While the importance of calcium in immune cell modulation has long been known, it is only in recent studies that immune cell differentiation, maturation and response to T cell receptor signaling, have been linked to the dynamics of calcium. Postantigen binding calcium signaling is controlled by the release of internal stores from the endoplasmatic reticulum (ER) and the opening of channels in the plasma membrane (PM). The release of calcium from the ER allow the stromal interaction molecule 1s (STIM1s) to dimerize and localize at the ER-PM junction where they are then able to bind to calcium releaseactivated calcium channel protein 1s (Orai1s) at the PM. This causes the Orai1 channels to become permeable to calcium, causing a flux across the membrane. It is unclear if STIM1 and Orai1 are directed to bind by some signaling mechanism or simply co-localize because of normal diffusion constraints of molecular motion. We here present a stochastic model of STIM1 and Orai1 movement and interaction and relate them to observed patterns seen pre and post activation of the T cell receptor. With this simulation we have taken a sampling rate of molecule locations, similar to experimental observation, and determined observed rates of diffusion based on individual molecules that we simulated within our analysis. Thanks to our mode of simulation, we can model how the movement of individual molecules and the influx of calcium appear at the population level post T cell stimulation. Through our model, we find that diffusion trap mechanics are sufficient to describe the observed STIM accumulation at the ER-PM junction and that the boundary conditions of a diffusion trap and the decrease in diffusion due to STIM-Orai conjugate formations could account fully for the observed decrease in the rate of STIM motion after ER calcium release." @default.
- W2405842331 created "2016-06-24" @default.
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- W2405842331 date "2015-07-01" @default.
- W2405842331 modified "2023-09-24" @default.
- W2405842331 title "A molecular model of STIM1-Orai1 movement and binding and their influence on calcium dynamics in T cell receptor response" @default.
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- W2405842331 doi "https://doi.org/10.1109/aisw.2015.7469234" @default.
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