%0 Journal Article %A Jean-Sébastien Teoh %A Wenyue Wang %A Gursimran Chandhok %A Roger Pocock %A Brent Neumann %T Development and maintenance of synaptic structure is mediated by the alpha-tubulin acetyltransferase MEC-17/αTAT1 %D 2019 %R 10.1101/522904 %J bioRxiv %P 522904 %X Microtubules are fundamental elements of neuronal structure and function. They are dynamic structures formed from protofilament chains of α- and β-tubulin heterodimers. Acetylation of the lysine 40 (K40) residue of α-tubulin protects microtubules from mechanical stresses by imparting structural elasticity. The enzyme responsible for this acetylation event is MEC-17/αTAT1. However, despite its functional importance, the consequences of MEC-17/αTAT1 misregulation on neuronal structure and function are incompletely defined. Using overexpression and loss of function approaches, we have analysed the effects of MEC-17 misregulation on the development and maintenance of synaptic branches in the mechanosensory neurons of Caenorhabditis elegans. We find that synaptic branch extension is delayed, and that synaptogenesis is defective in these animals. Strikingly, by adulthood the synaptic branches specifically and spontaneously degenerate. This phenotype is dependent on the acetyltransferase domain on MEC-17, revealing that correct levels of K40 acetylation are essential for the maintenance of neuronal structure. Finally, we investigate the genetic pathways in which mec-17 functions, uncovering novel interactions with dual leucine-zipper kinase dlk-1 and the focal adhesion gene zyx-1/Zyxin. These interactions link MEC-17 together with factors involved in neuronal and actin remodelling to protect synaptic branches. Together, our results reveal that appropriate levels of α-tubulin K40 acetylation by MEC-17 are crucial for the development and maintenance of neuronal architecture. %U https://www.biorxiv.org/content/biorxiv/early/2019/01/16/522904.full.pdf