RT Journal Article
SR Electronic
T1 Acetylated α-tubulin residue K394 regulates microtubule stability to shape the growth of axon terminals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.01.438108
DO 10.1101/2021.04.01.438108
A1 Harriet A. J. Saunders
A1 Dena M. Johnson-Schlitz
A1 Brian V. Jenkins
A1 Peter J. Volkert
A1 Sihui Z. Yang
A1 Jill Wildonger
YR 2021
UL http://biorxiv.org/content/early/2021/04/02/2021.04.01.438108.abstract
AB Microtubules are essential to neuron shape and function. Therefore, the stability of the microtubule cytoskeleton must be carefully regulated. Acetylation of tubulin has the potential to directly tune microtubule stability, and proteomic studies have identified several acetylation sites in α-tubulin. This includes the highly conserved residue lysine 394 (K394), which is located at the αβ-tubulin dimer interface. Using a fly model, we show that α-tubulin K394 is acetylated in the nervous system and is an essential residue. We found that an acetylation-blocking mutation in endogenous α-tubulin, K394R, perturbs the synaptic morphogenesis of motoneurons by reducing microtubule stability. Intriguingly, the K394R mutation has opposite effects on the growth of two functionally and morphologically distinct motoneurons, revealing neuron-type-specific responses when microtubule stability is altered. Eliminating the deacetylase HDAC6 increases K394 acetylation, and the over-expression of HDAC6 reduces microtubule stability similar to the K394 mutant. Thus, our findings implicate α-tubulin K394 and its acetylation in the regulation of microtubule stability and suggest that HDAC6 regulates K394 acetylation during synaptic morphogenesis.Competing Interest StatementThe authors have declared no competing interest.