The Ca2+ selective channel ORAI1 and endoplasmic reticulum (ER)-resident STIM proteins
form the core of the channel complex mediating store operated Ca2+ entry (SOCE). Using liquid phase
electron microscopy (LPEM), the distribution of ORAI1 proteins was examined at rest and after SOCEactivation at nanoscale resolution. The analysis of over seven hundred thousand ORAI1 positions
revealed a number of ORAI1 channels had formed STIM-independent distinct supra-molecular
clusters. Upon SOCE activation and in the presence of STIM proteins, a fraction of ORAI1 assembled
in micron-sized two-dimensional structures, such as the known puncta at the ER plasma membrane
contact zones, but also in divergent structures such as strands, and ring-like shapes. Our results thus
question the hypothesis that stochastically migrating single ORAI1 channels are trapped at regions
containing activated STIM, and we propose instead that supra-molecular ORAI1 clusters fulfill an
amplifying function for creating dense ORAI1 accumulations upon SOCE-activation
