The N terminus of Orai1 couples to the AKAP79 signaling complex to drive NFAT1 activation by local Ca <sup>2+</sup> entry
Pulak Kar, Yu‐Ping Lin, Rajesh Bhardwaj, Charles J. Tucker, Gary S. Bird, Matthias A. Hediger, Carina Mónico, Nader Amin, Anant B. Parekh
Abstract
Significance Store-operated Orai1 Ca 2+ channels are a major route for trigger Ca 2+ in immune cells. Local Ca 2+ entry through the channels activates NFAT transcription factors, which in turn increase expression of chemokines and cytokines that orchestrate inflammatory responses. We identify a region on the N terminus of Orai1 that is indispensable for activating NFAT, through interaction with the scaffolding protein AKAP79. We show that a peptide that uncouples Orai1 from AKAP79 suppresses cytokine production, leaving other functional consequences of the channel intact. Our results identify an approach for developing immunosuppressant drugs.