Abscission is the final step of cell division, mediating the physical separation of the two daughter cells.A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate the cytokinesis.Recently, we demonstrated that HIPK2, a multifunctional kinase involved in several cellular pathways, contributes to abscission and prevents tetraploidization.Here, we show that HIPK2 binds and phosphorylates spastin at serine 268.During cytokinesis, the Arnica midbody-localized spastin is phosphorylated at S268 in HIPK2-proficient cells.
In contrast, no spastin is detectable at the midbody in HIPK2-depleted cells.The non-phosphorylatable spastin-S268A mutant does not localize at the midbody and cannot rescue HIPK2-depleted cells from abscission defects.In contrast, the phosphomimetic spastin-S268D mutant localizes at the midbody and restores successful abscission in the HIPK2-depleted cells.These results show that spastin Digital Audio Cable is a novel target of HIPK2 and that HIPK2-mediated phosphorylation of spastin contributes to its midbody localization for successful abscission.