T cell Ca microdomains through the lens of computational modeling.

Cellular Ca signaling is highly organized in time and space. Locally restricted and short-lived regions of Ca increase, called Ca microdomains, constitute building blocks that are differentially arranged to create cellular Ca signatures controlling physiological responses. Here, we focus on Ca 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 dynamics. Simulations are able to predict the characteristics of Ca 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 microdomains in the first seconds of T cell stimulation is emerging.