@article {Peckys2020.01.13.903856, author = {Diana B. Peckys and Dalia Alansary and Barbara. A. Niemeyer and Niels de Jonge}, title = {ORAI1 channels form supra-molecular clusters at rest and agglomerate into distinct plasma membrane areas of oval and strand-like shapes after activation}, elocation-id = {2020.01.13.903856}, year = {2020}, doi = {10.1101/2020.01.13.903856}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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 SOCE-activation at nanoscale resolution. The analysis of over seven hundred thousand of ORAI1 positions showed that already at rest, a majority of the ORAI1 channels formed STIM-independent distinct supra-molecular clusters. Upon SOCE activation and in the presence of STIM proteins, ORAI1 assembled in micron-sized two-dimensional (2D) structures, such as the known punctae 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.}, URL = {https://www.biorxiv.org/content/early/2020/01/14/2020.01.13.903856}, eprint = {https://www.biorxiv.org/content/early/2020/01/14/2020.01.13.903856.full.pdf}, journal = {bioRxiv} }