Revealing the dynamic landscape of posttranslational modifications of cytoskeletal proteins under redox stress

A work recently published in the journal Redox Biology by the group of Dr. Dolores Pérez-Sala at the Centro de Investigaciones Biológicas Margarita Salas unveils a multiplicity of posttranslational modifications in vimentin, actin, and tubulin, which occur under cellular redox stress and recovery in a dynamic manner, in connection with a fast and pronounced cytoskeletal reorganization.

The cytoskeleton is a supramolecular structure consisting of interacting protein networks that support not only cell dynamics in essential processes such as migration and division, but also act in response to stress. Fast cytoskeletal remodeling can be achieved with the participation of regulatory proteins and posttranslational modifications (PTMs).

In this work, primary cardiac cells were subjected to mild redox stress with a single oxidant. Fluorescence microscopy shows how cytoskeletal networks of f-actin, microtubules, and vimentin filaments respond to and recover from this stress. Additionally, high-resolution mass spectrometry illustrates that this transient reorganization of the cytoskeleton is paralleled by dynamic changes in the landscape of posttranslational modifications on actin, tubulin, and vimentin, in a target-, residue- and reactive species-dependent manner. 

Griesser et al. mapped sixty-two different PTMs on these proteins, unveiling the occurrence of a “chain reaction” with the generation of multiple reactive species under stress, as well as the existence of protein hot spots for modification with potential importance in signaling and crosstalk. Moreover, the identification of several novel PTMs in these proteins paves the way for unveiling new cytoskeleton regulatory mechanisms.

The work is the result of an international collaboration between the groups of Dolores Pérez-Sala (CIB-Margarita Salas) and Maria Fedorova (Leipzig University) which has been developed in the context of the ITN Masstrplan MSCA grant nº 675132, H2020, and COST Actions CM1001 and CA19105 EpiLipidNet.

Reference: Dynamic posttranslational modifications of cytoskeletal proteins unveil hot spots under nitroxidative stress. Griesser E, Vemula V, Mónico A, Pérez-Sala D, Fedorova M. Redox Biol. 2021 May 24;44:102014. doi: 10.1016/j.redox.2021.102014. Online ahead of print. PMID: 34062408