Non-enzymatic Activity of the ?-Tubulin Acetyltransferase ?TAT Limits Synaptic Bouton Growth in Neurons.

ABSTRACT: Neuronal axons terminate as synaptic boutons that form stable yet plastic connections with their targets. Synaptic bouton development relies on an underlying network of both long-lived and dynamic microtubules that provide structural stability for the boutons while also allowing for their growth and remodeling. However, a molecular-scale mechanism that explains how neurons appropriately balance these two microtubule populations remains a mystery. We hypothesized that ?-tubulin acetyltransferase (?TAT), which both stabilizes long-lived microtubules against mechanical stress via acetylation and has been implicated in promoting microtubule dynamics, could play a role in this process. Using the Drosophila neuromuscular junction as a model, we found that non-enzymatic d?TAT activity limits the growth of synaptic boutons by affecting dynamic, but not stable, microtubules. Loss of d?TAT results in the formation of ectopic boutons. These ectopic boutons can be similarly suppressed by resupplying enzyme-inactive d?TAT or by treatment with a low concentration of the microtubule-targeting agent vinblastine, which acts to suppress microtubule dynamics. Biophysical reconstitution experiments revealed that non-enzymatic ?TAT1 activity destabilizes dynamic microtubules but does not substantially impact the stability of long-lived microtubules. Further, during microtubule growth, non-enzymatic ?TAT1 activity results in increasingly extended tip structures, consistent with an increased rate of acceleration of catastrophe frequency with microtubule age, perhaps via tip structure remodeling. Through these mechanisms, ?TAT enriches for stable microtubules at the expense of dynamic ones. We propose that the specific suppression of dynamic microtubules by non-enzymatic ?TAT activity regulates the remodeling of microtubule networks during synaptic bouton development.

SUBMITTER: Coombes CE 

PROVIDER: S-EPMC7047862 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature