SUMOylation of α-tubulin is a novel modification regulating microtubule dynamics

Microtubules (MTs) are regulated by a number of known posttranslational modifications (PTMs) on alpha/beta-tubulin to fulfill diverse cellular functions. Here, we showed that SUMOylation is a novel PTM on alpha-tubulin in vivo and in vitro. The SUMOylation on alpha-tubulin mainly occurred at Lys 96 (K96), K166, and K304 of soluble alpha-tubulin and could be removed by small ubiquitin-related modifier (SUMO)-specific peptidase 1. In vitro experiments showed that tubulin SUMOylation could reduce interprotofilament interaction, promote MT catastrophe, and impede MT polymerization. In cells, mutation of the SUMOylation sites on alpha-tubulin reduced catastrophe frequency and increased the proportion of polymerized alpha-tubulin, while upregulation of SUMOylation with fusion of SUMO1 reduced alpha-tubulin assembly into MTs. Additionally, overexpression of SUMOylation-deficient alpha-tubulin attenuated the neurite extension in Neuro-2a cells. Thus, SUMOylation on alpha-tubulin represents a new player in the regulation of MT properties.