Three-dimensional spatio-temporal modelling of store operated Ca2+ entry: insights into ER refilling and the spatial signature of Ca2+ signals

McIvor, Emma; Coombes, Stephen; Thul, Ruediger

Abstract

The spatial organisation of Orai channels and SERCA pumps within ER-PM junctions is important for enhancing the versatility and specificity of subcellular Ca2+ signals generated during store operated Ca2+ entry (SOCE). In this paper we present a novel three dimensional spatio-temporal model describing Ca2+ dynamics in the ER-PM junction and sub-PM ER during SOCE. We investigate the role of Orai channel and SERCA pump location to provide insights into how these components shape the Ca2+ signals generated and affect ER refilling. We find that the organisation of Orai channels within the ER-PM junction controls the amplitude and shape of the Ca2+ profile but does not enhance ER refilling. The model shows that ER refilling is only weakly affected by the location of SERCA2b pumps within the ER-PM junction and that the placement of SERCA2a pumps within the ER-PM junction has much greater control over ER refilling.

Citation

McIvor, E., Coombes, S., & Thul, R. (2018). Three-dimensional spatio-temporal modelling of store operated Ca2+ entry: insights into ER refilling and the spatial signature of Ca2+ signals. Cell Calcium, 73, https://doi.org/10.1016/j.ceca.2018.03.006

• Journal Article Type: Article
• Acceptance Date: Mar 30, 2018
• Online Publication Date: Apr 4, 2018
• Publication Date: Jul 31, 2018
• Deposit Date: Apr 16, 2018
• Publicly Available Date: Apr 5, 2019
• Journal: Cell Calcium
• Print ISSN: 0143-4160
• Electronic ISSN: 1532-1991
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 73
• DOI: https://doi.org/10.1016/j.ceca.2018.03.006
• Keywords: Calcium signalling; ER-PM junctions; Mathematical modelling; Spatial Ca2+ signature; Orai channels; ER refilling
• Public URL: https://nottingham-repository.worktribe.com/output/948273
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0143416018300149
• Contract Date: Apr 16, 2018