Conclusion
We showed that Dock5 is a new regulator of microtubule dynamic instability in osteoclast. Significance: Dock5 dual role in the regulation of the actin cytoskeleton and microtubule, which both need to be intact for bone resorption, reinforces the fact that it is an interesting therapeutic target for osteolytic pathologies.
Results
In this report, we show that Dock5 knockout osteoclasts also present a reduced acetylated tubulin level leading to a decreased length and duration of microtubule growth phases, whereas their growth speed remains unaffected. Dock5 does not act by direct interaction with the polymerised tubulin. Using specific Rac inhibitors, we showed that Dock5 regulates microtubule dynamic instability through Rac-dependent and -independent pathways. The latter involves GSK3β inhibitory serine 9 phosphorylation downstream of Akt activation but not HDAC6 activity.
Significance
Dock5 dual role in the regulation of the actin cytoskeleton and microtubule, which both need to be intact for bone resorption, reinforces the fact that it is an interesting therapeutic target for osteolytic pathologies.