Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation
- 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.
Document Type: | Article |
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Author: | Diana B. PeckysORCiD, Daniel Gaa, Dalia AlansaryORCiD, Barbara A. NiemeyerORCiD, Niels de JongeORCiD |
URN: | urn:nbn:de:bsz:291:415-814 |
DOI: | https://doi.org/10.3390/ijms22020799 |
Parent Title (English): | International journal of molecular sciences |
Volume: | 22 |
Issue: | 2 |
First Page: | 799 |
Language: | English |
Year of first Publication: | 2021 |
Release Date: | 2022/08/09 |
Tag: | calcium channel; liquid phase electron microscopy; membrane protein; protein clusters; single molecule |
Impact: | 06.208 (2021) |
Funding Information: | Deutsche Forschungsgemeinschaft (SFB1027 (project C7)) |
Scientific Units: | Innovative Electron Microscopy |
DDC classes: | 500 Naturwissenschaften und Mathematik / 530 Physik |
Open Access: | Open Access |
Signature: | INM 2021/014 |
Licence (German): | ![]() |