STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca <sup>2+</sup> entry with NFAT1 activation
Ga‐Yeon Son, Krishna Prasad Subedi, Hwei Ling Ong, Lucile Noyer, Hassan Saadi, Changyu Zheng, Rajesh Bhardwaj, Stefan Feske, Indu S. Ambudkar
Abstract
Significance Ca 2+ entry mediated by the plasma membrane (PM) channel Orai1 controls nuclear factor of activated T cells 1 (NFAT1)-dependent gene expression that regulates critical cellular functions. Ca 2+ -sensing endoplasmic reticulum (ER) proteins, STIM1 and STIM2, regulate Orai1 function in response to decreases in [Ca 2+ ] ER . While STIM1 is the primary regulator of Orai1 activity, STIM2 has a minor contribution to Ca 2+ entry but is relevant for Ca 2+ -dependent NFAT1 activation. Here we report that STIM2 recruits Orai1/STIM1 to ER-PM junctions and promotes channel assembly with the AKAP79 signaling complex. The latter is an important step that allows Ca 2+ entry mediated by Orai1 to be specifically used for NFAT1 activation. Our findings reveal that STIM2 enhances the coupling of Orai1 function with NFAT1 activation.