Dynamin 2 associates with microtubules at mitosis and regulates cell cycle progression

Abstract

Dynamin, a ~100 kDa large GTPase, is known as a key player for membrane traffic. Recent evidence shows that dynamin also regulates dynamic instability of microtubules by a mechanism independent of membrane traffic. As microtubules are highly dynamic during mitosis, we investigated whether the regulation of microtubules by dynamin is essential for cell cycle progression. Dynamin 2 intensely localized at the mitotic spindle, and the localization depended on its proline-rich domain (PRD), which is required for microtubule association. The deletion of PRD resulted in the impairment of cytokinesis, whereas the mutant had less effect on endocytosis. Interestingly, dominant-negative dynamin (K44A), which blocks membrane traffic but has no effect on microtubules, also blocked cytokinesis. On the other hand, deletion of middle domain, which binds to g-tubulin, impaired the entry into mitosis. As both deletion mutants had no significant effect on endocytosis, dynamin2 may participate in cell cycle progression by regulating the microtubules. These data suggest that dynamin may play a key role for cell cycle progression by two distinct pathway, membrane traffic and cytoskeleton.