Loss of Tubulin Tyrosination in Purkinje Neurons Does Not Cause Their Degeneration

Abstract

Posttranslational modifications (PTMs) of tubulin have been suggested to form a tubulin code to coordinate microtubule functions. While at the molecular level PTMs were demonstrated to act in a target-specific manner, an outstanding question is the selectivity with which they control cellular and physiological functions. For instance, several tubulin PTMs have been linked to neurodegeneration, suggesting that whichever PTM is dysregulated could be sufficient to induce microtubule perturbation and cause neuronal death. Here we test whether perturbation of tyrosination can cause degeneration of Purkinje neurons similar to what happens when the PTM polyglutamylation is abnormally accumulated. Strikingly, this is not the case: deletion of tubulin tyrosine ligase in Purkinje cells, while resulting in loss of tyrosinated tubulin in these neurons, does not affect their survival nor function for more than one year. Our results thus reveal a highly specific role of polyglutamylation in neuronal homeostasis that is not replicated by other tubulin PTMs, suggesting stringent functional specialisation of those PTMs at the physiological level.