Type III intermediate filaments as targets and effectors of electrophiles and oxidants.

摘要: Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin glial fibrillary acidic protein (GFAP), targets for diverse modifications oxidants electrophiles, which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these include lipoxidation senescence rheumatoid arthritis, disulfide formation cataracts nitrosation endothelial shear stress, although some oxidative can also be detected under basal conditions. We previously proposed that residues vimentin GFAP act sensors electrophilic hinges influencing filament assembly. Accumulating evidence indicates the structurally modifications, either per se or combination with other elicit specific functional outcomes inducing distinct assemblies network rearrangements, including stabilization, bundling fragmentation. Cysteine-deficient mutants protected from alterations but show compromised cellular performance expansion, organelle positioning aggresome formation, revealing importance this residue. Therefore, high susceptibility to modification IFs its cornerstone position architecture sustains role redox sensing integration responses. This has deep pathophysiological implications supports potential drug target.