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- W2946982829 abstract "Abstract Background information Osteoclast resorption is dependent on a podosome-rich structure, called sealing zone, which is stabilized by acetylated microtubules. It tightly attaches the osteoclast to the bone creating a favorable acidic microenvironment for bone degradation. We already established that Rac activation by Dock5 is necessary for osteoclast resorption. Indeed, inhibition of Dock5 in osteoclasts results in Rac1 decreased activity associated to impaired podosome assembly into sealing zones and resorbing activity. 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 polymerized tubulin but through inhibition of the microtubules destabilizing kinase GSK3β downstream of Akt activation. Interestingly, we ruled out the implication of Rac1 in this process using specific inhibitors. Conclusion Our data involve Dock5 as a new regulator of microtubule dynamic instability in osteoclast. Significance The fact that Dock5 is a regulator of both actin cytoskeleton and microtubule dynamics makes it an interesting therapeutic target for osteolytic pathologies because of its dual role on sealing zone formation and stabilization." @default.
- W2946982829 created "2019-06-07" @default.
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- W2946982829 date "2019-05-29" @default.
- W2946982829 modified "2023-09-27" @default.
- W2946982829 title "Dock5 is a new regulator of microtubule dynamic instability through GSK3β inhibition in osteoclasts" @default.
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- W2946982829 doi "https://doi.org/10.1101/653055" @default.
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