Emerging Roles of Tubulin Isoforms and Their Post-Translational Modifications in Microtubule-Based Transport and Cellular Functions

Microtubules are hollow cylindrical polymers made up of tubulin. This heterodimeric protein, tubulin, exists in multiple forms: tubulin isotypes and tubulin isoforms. Distinct α- and β-tubulin genes give rise to tubulin isotypes, which differ in their amino acid sequences and cellular expression patterns. The tubulin post-translational modifications (PTMs) encode regulatory information within the microtubule lattice, modifying its biophysical characteristics and shaping interactions with motor proteins and microtubule-associated proteins. Different tubulin isotype compositions and post-translational modification patterns generate distinct tubulin isoforms. These isoforms are tissue-specific and regulate the functions of microtubules in specialized cells and cellular components such as cilia. Tubulin isoforms control cellular transport, regulate mechanosensitivity and shape the cytoskeleton, impacting the cellular functions and homeostasis. This review discusses the tubulin PTMs, including acetylation, methylation, palmitoylation, polyamination, glutamylation, glycylation, tyrosination, phosphorylation, SUMOylation, and ubiquitination, with emphasis on how isotype diversity and PTM-driven regulation together modulate microtubule behaviour, intracellular transport, and cellular functions.