c-Abl kinase-mediated phosphorylation of -tubulin promotes -tubulin ring complexes assembly and microtubule nucleation

Cytoskeletal microtubules (MTs) are nucleated from gamma-tubulin ring complexes (gamma TuRCs) located at MT organizing centers (MTOCs), such as the centrosome. However, the exact regulatory mechanism of gamma TuRC assembly is not fully understood. Here, we showed that the nonreceptor tyrosine kinase c-Abl was associated with and phosphorylated gamma-tubulin, the essential component of the gamma TuRC, mainly on the Y443 residue by in vivo (immunofluorescence and immunoprecipitation) or in vitro (surface plasmon resonance) detection. We further demonstrated that phosphorylation deficiency significantly impaired gamma TuRC assembly, centrosome construction, and MT nucleation. c-Abl/Arg deletion and gamma-tubulin Y443F mutation resulted in an abnormal morphology and compromised spindle function during mitosis, eventually causing uneven chromosome segregation. Our findings reveal that gamma TuRC assembly and nucleation function are regulated by Abl kinase-mediated gamma-tubulin phosphorylation, revealing a fundamental mechanism that contributes to the maintenance of MT function.