Molecular Determinants of the Coupling between STIM1 and Orai Channels

• DOI: 10.1074/jbc.m109.018408
• Publication Date: 2009-06-09T01:54:50Z
• Authors: Irene Frischauf; Martin Muik; Isabella Derler; Judith Bergsmann; Marc Fahrner; Rainer Schindl; Klaus Groschner; Christoph Romanin
• Keywords: Orai1; Coiled coil; C-terminus

STIM1 and Orai1 have been reported to interact upon store depletion culminating in Ca(2+) release-activated current activation. Recently, the essential region has identified within C terminus that includes second coiled-coil domain C-terminally extended by approximately 50 amino acids exhibits a strong binding terminus. Based on homology Orai family, an analogous scenario might be assumed for Orai2 as well Orai3 channels both are activated similar STIM1-dependent manner. A combined approach of electrophysiology Foerster resonance energy transfer microscopy uncovered general mechanism communication with proteins involved conserved putative domains respective motif single mutation abrogated terminus, whereas still allowed their moderate However, increasing probability gain function deletion or generating Orai1-Orai3 chimera containing recovered stimulation extent Orai2/3. At level STIM1, decreasing abolished activation but enabled partial Orai2/3 channels. double fully disrupted all three In aggregate, impairment overall between probabilities either one termini compatible concept functional, heteromeric interaction.