Figure 8: Ca²⁺ entry/clearance coupling increases NFAT activation.

Model of the results and proposed mechanism. During T cell activation, InsP₃-induced store depletion leads to the activation of STIM1 and Ca²⁺ influx through Orai1. Without recruitment and regulation of PMCA4b function by STIM1 and POST (A), Orai1 channels allow Ca²⁺ influx, followed by Ca²⁺-dependent inactivation of the channel. NFAT activation is limited by the large but transient activation of Orai1. Recruitment of POST and PMCA4b to the IS with STIM1 and Orai1 (B) leads to extrusion of Ca²⁺ in the immediate vicinity of Orai1. This prevents Ca²⁺-dependent inactivation of Orai1 facilitating greater NFAT activation.