Stress-induced changes in the S-palmitoylation and S-nitrosylation of synaptic proteins

Abstract

The precise regulation of synaptic integrity is critical for neuronal network connectivity and proper brain function. Essential aspects of the activity and localization of synaptic proteins are regulated by posttranslational modifications. S-palmitoylation is a reversible covalent modification of the cysteine with palmitate. It modulates affinity of the protein for cell membranes and membranous compartments. Intracellular palmitoylation dynamics are regulated by other posttranslational modifications, such as S-nitrosylation. Still unclear, however, are the ways in which this crosstalk is affected in brain pathology, such as stress-related disorders. Using a newly developed mass spectrometry-based approach (Palmitoylation And Nitrosylation Interplay Monitoring), we analyzed the endogenous S-palmitoylation and S-nitrosylation of postsynaptic density proteins at the level of specific single cysteines in a mouse model of chronic stress. Our results suggest that atypical mechanism of crosstalk between the S-palmitoylation and S-nitrosylation of synaptic proteins might be one of the major events associated with chronic stress disorders.