Axon growth is under tight control to establish the functional neural circuits during brain development in mammalian. Microtubule, which is a highly dynamic cytoskeletal structure, is composed of α- and β-tubulin heterodimers, post-translational modifications of tubulin is important in regulating the organization and dynamics of microtubules. Despite the belief that cytoskeletal dynamics is critical for cell morphology, the role of microtubule acetylation in axon development in the mammalian central nervous system remains unclear.
WEI Dan, GAO Nannan and their colleagues, under the supervision of Dr. BAO Lan at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, found that loss of α-tubulin acetylation in MEC-17 knockout mice leads to axon overbranching and overgrowth both in vivo and in vitro, and this effect can be rescued by the re-expression of MEC-17 or of acetylation-mimicking α-tubulinK40Q but not of MEC-17F183A, which lacks α-tubulin acetyltransferase activity, in cultured MEC-17-deficient neurons. Moreover, loss of α-tubulin acetylation in the neuron increases microtubule plus-end dynamics and microtubule debundling along the axon shaft and allows microtubules to easily invade filopodia and growth cones. Taxol application dampened microtubule hyperdynamics and suppressed axon overbranching and overgrowth in MEC-17-deficient neurons. These findings reveal that α-tubulin acetylation acts as a brake for axon overbranching and overgrowth by dampening microtubule dynamics, providing insight into the role of microtubule post-translational modifications in regulating neural development.
This work entitled “α-Tubulin Acetylation Restricts Axon Overbranching by Dampening Microtubule Plus-End Dynamics in Neurons” was published online in Cerebral Cortex on Sep. 12, 2017. This work was collaborated with ZHANG Xu in the Institute of Neuroscience, Chinese Academy of Sciences.
This study was supported by the grants from the National Natural Science Foundation of China, National Basic Research Program of China and Strategic Priority Research Program of the Chinese Academy of Sciences.
AUTHOR CONTACT:
BAO Lan, Principal Investigator
Institute of Biochemistry and Cell Biology,
Chinese Academy of Sciences
Shanghai 200031, China
Phone: 86-21-54921369
E-mail: baolan@sibcb.ac.cn
A model of α-tubulin acetylation in regulating microtubule dynamics in nascent branches and growth cones during axon development
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