Tubulin posttranslational modifications through the lens of new technologies

The Tubulin Code revolutionizes our understanding of microtubule dynamics and functions, proposing a nuanced system governed by tubulin isotypes, posttranslational modifications (PTMs) and microtubule-associated proteins (MAPs). Tubulin isotypes, diverse across species, contribute structural complexity, and are thought to influence microtubule functions. PTMs encode dynamic information on microtubules, which are read by several microtubule interacting proteins and impact on cellular processes. Here we discuss recent technological and methodological advances, such as in genome engineering, live cell imaging, expansion microscopy, and cryo-electron microscopy that reveal new elements and levels of complexity of the tubulin code, including new modifying enzymes and nanopatterns of PTMs on individual microtubules. The Tubulin Code’s exploration holds transformative potential, guiding therapeutic strategies and illuminating connections to diseases like cancer and neurodegenerative disorders, underscoring its relevance in decoding fundamental cellular language.