Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease

Abstract

Neurons are equipped with microtubules of different stability with stable and dynamic domains often coexisting on the same microtubule. While dynamic microtubules undergo random transitions between disassembly and assembly, stable ones persist long enough to serve as platforms for tubulin-modifying enzymes (known as writers) that attach molecular components to the α- or β-tubulin subunits. The combination of these posttranslational modifications (PTMs) results in a “tubulin code,” dictating the behavior of selected proteins (known as readers), some of which were shown to be crucial for neuronal function. Recent research has further highlighted that disturbances in tubulin PTMs can lead to neurodegeneration, sparking an emerging field of investigation with numerous questions such as whether and how tubulin PTMs can affect neurotransmission and synaptic plasticity and whether restoring balanced tubulin PTM levels could effectively prevent or mitigate neurodegenerative disease.