Alteration of stress granule formation and clearance by <i>S</i>-Nitrosylation modification of G3BP1

Abstract

Nitric oxide (NO) is a signaling molecule that exerts a variety of regulatory functions in physiological states and stress responses. NO has been proposed to modulate protein function through S-nitrosylation of cysteine thiol residues in proteins. Appropriate amounts of NO result in neuroprotective effects via increasing moderate S-nitrosylated proteins and the cGMP pathway. On the other hand, excess amounts of NO promote neurodegenerative signaling pathways by increasing aberrant S-nitrosylated proteins.We found that Ras GTPase-activating protein-binding protein 1 (G3BP1), which forms stress granules (SGs) implicated in neurodegenerative diseases, was a target of S-nitrosylation. Treatment with NO stimulated this modification in a concentration-dependent manner. It has been known that SGs are rapidly formed by oxidative and heat shock stresses. In addition, SGs formation induced by proteasome inhibitor (MG132) was gradually degraded, whereas NO delayed this degradation. These findings suggest that S-nitrosylated G3BP1 not only promotes SGs formation but also delays SGs clearance.