Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation

International Journal of Molecular Sciences

Niels de Jonge¹  Daniel Gaa¹  Dalia Alansary²  Barbara A. Niemeyer²  Diana B. Peckys² 

[1] INM—Leibniz Institute for New Materials, 66123 Saarbrücken, Germany;Molecular Biophysics, Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany;

关键词: calcium channel;    protein clusters;    membrane protein;    liquid phase electron microscopy;    single molecule;    correlative microscopy;   

DOI  :  10.3390/ijms22020799

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown