Synergistic stabilization by nitrosoglutathione-induced thiol modifications in the stromal interaction molecule-2 luminal domain suppresses basal and store operated calcium entry.

ABSTRACT: Stromal interaction molecule-1 and -2 (STIM1/2) are endoplasmic reticulum (ER) membrane-inserted calcium (Ca²⁺) sensing proteins that, together with Orai1-composed Ca²⁺ channels on the plasma membrane (PM), regulate intracellular Ca²⁺ levels. Recent evidence suggests that S-nitrosylation of the luminal STIM1 Cys residues inhibits store operated Ca²⁺ entry (SOCE). However, the effects of thiol modifications on STIM2 during nitrosative stress and their role in regulating basal Ca²⁺ levels remain unknown. Here, we demonstrate that the nitric oxide (NO) donor nitrosoglutathione (GSNO) thermodynamically stabilizes the STIM2 Ca²⁺ sensing region in a Cys-specific manner. We uncovered a remarkable synergism in this stabilization inv

SUBMITTER: Novello MJ 

PROVIDER: S-EPMC7311479 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature