Orai channel GOF mutants define critical functional distinctions between Orai subtypes

Abstract

Store-operated calcium entry (SOCE) is a powerful mechanism controlling multiple physiological processes including transcription, cell proliferation, apoptosis, and secretion. PM Orai channels are activated by the ER Ca2+-sensing protein STIM, which induce channel conformational change that leads to gating. The gain of function (GOF) mutation Orai1-P245L, recognized to cause Stormorken-like syndrome, is known to have Ca2+ entry that’s independent of STIM activation due to the straightening of the Pro residue in the 4th transmembrane (TM4).