Deciphering the landscape of post-translational modifications in the centrosome upon T cell activation

Abstract

The shift from quiescent to effector T cells (TC) is controlled at the translational level. Post-translational modifications (PTMs) are key factors in the diversification of protein function. Advancements in mass spectrometry-based proteomics enable proteome-wide, hypothesis-free quantitative PTM analysis. Current research highlights the centrosome role in TC activation. Here the diversity of PTMs in the TC centrosome is studied by analyzing centrosome-enriched fractions from human resting and activated T lymphoblasts. Our results show that oxidative modifications predominate in this organelle, with tryptophan as the most frequently oxidized residue. These PTMs are enriched in proteins involved in translation, vesicular trafficking, cytoskeleton organization, among others. We also demonstrate the existence of PTM changes on specific protein regions during TC activation in Myh9 (hyperoxidized), and Gzma (hypoxidized). These hyper- or hypoxidized proteins display distinct functional distributions. Our study provides the first comprehensive PTM mapping of the TC centrosome, underscoring the PTM regulatory role in TC activation.