T cell Ca(2+) microdomains through the lens of computational modeling

Cellular Ca(2+) signaling is highly organized in time and space. Locally restricted and short-lived regions of Ca(2+) increase, called Ca(2+) microdomains, constitute building blocks that are differentially arranged to create cellular Ca(2+) signatures controlling physiological responses. Here, we focus on Ca(2+) microdomains occurring in restricted cytosolic spaces between the plasma membrane and the endoplasmic reticulum, called endoplasmic reticulum-plasma membrane junctions. In T cells, these microdomains have been finely characterized. Enough quantitative data are thus available to develop detailed computational models of junctional Ca(2+) dynamics. Simulations are able to predict the characteristics of Ca(2+) increases at the level of single channels and in junctions of different spatial configurations, in response to various signaling molecules. Thanks to the synergy between experimental observations and computational modeling, a unified description of the molecular mechanisms that create Ca(2)(+) microdomains in the first seconds of T cell stimulation is emerging.