TY - JOUR U1 - Wissenschaftlicher Artikel A1 - Peckys, Diana B. A1 - Gaa, Daniel A1 - Alansary, Dalia A1 - Niemeyer, Barbara A. A1 - de Jonge, Niels T1 - Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation JF - International journal of molecular sciences N2 - 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 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. KW - calcium channel KW - protein clusters KW - membrane protein KW - liquid phase electron microscopy KW - single molecule Y1 - 2021 UN - https://nbn-resolving.org/urn:nbn:de:bsz:291:415-814 U6 - https://doi.org/10.3390/ijms22020799 DO - https://doi.org/10.3390/ijms22020799 VL - 22 IS - 2 SP - 799 ER -