alphatubulin

Alpha-tubulin is a core component of the tubulin protein family that forms microtubules, the hollow, filamentous structures of the cytoskeleton in most eukaryotic cells. It exists as part of a heterodimer with beta-tubulin, and these dimers polymerize to build microtubules essential for maintaining cell shape, enabling intracellular transport, and ensuring proper chromosome segregation during cell division. In humans, several alpha-tubulin isotypes are encoded by distinct genes, including TUBA1A, TUBA1B, TUBA1C, and TUBA8, with tissue- and development-specific expression patterns.

Biochemically, alpha- and beta-tubulin assemble into a GTP-bound heterodimer. The alpha-tubulin subunit binds GTP at a non-exchangeable site that is not hydrolyzed during polymerization, while beta-tubulin carries a GTP site that is hydrolyzed to GDP after the dimer is incorporated into the microtubule. Dimers align to form protofilaments, which typically associate into a microtubule composed of about 13 protofilaments. Microtubule dynamics are driven by GTP hydrolysis, and by factors such as temperature and microtubule-associated proteins.

Post-translational modifications of alpha-tubulin, including acetylation at lysine 40, detyrosination/tyrosination, and polyglutamylation, influence microtubule stability and interactions with motor proteins and other MAPs. Differences among alpha-tubulin isotypes can affect modification patterns and function, contributing to specialized microtubule roles in various cell types.

Functionally, alpha-tubulin participates in mitosis, meiosis, axonal and dendritic transport, and ciliogenesis. Mutations or dysregulation of alpha-tubulin genes are associated with neurodevelopmental disorders and brain malformations, reflecting the critical role of microtubules in neural development and cellular organization. The protein is highly conserved across eukaryotes, underscoring its fundamental cellular importance.