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High glucose distinctively regulates Ca2+ influx in cytotoxic T lymphocytes upon target recognition and thapsigargin stimulation
2020, Zou, Huajiao, Yang, Wenjuan, Schwär, Gertrud, Zhao, Renping, Alansary, Dalia, Yin, Deling, Schwarz, Eva C., Niemeyer, Barbara A., Qu, Bin
In CTLs: High glucose‐culture enhances thapsigargin‐induced SOCE but decreases target recognition‐induced Ca2+ influx. High glucose‐culture regulates expression of ORAIs and STIMs without affecting glucose uptake. More high glucose‐cultured CTLs are prone to necrosis after execution of killing.
Supra-Molecular Assemblies of ORAI1 at Rest Precede Local Accumulation into Puncta after Activation
2021, Peckys, Diana B., Gaa, Daniel, Alansary, Dalia, Niemeyer, Barbara A., de Jonge, Niels
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.