detyrosinationtyrosination

Detyrosinationtyrosination refers to the detyrosination–tyrosination cycle of alpha-tubulin, a reversible post-translational modification that modulates microtubule properties. In detyrosination, the C-terminal tyrosine residue of alpha-tubulin is removed, generating detyrosinated tubulin. The reverse step, tyrosination, adds a tyrosine back onto the tubulin by the action of tubulin tyrosine ligase (TTL). This cycle operates on tubulin that is part of microtubules as well as soluble tubulin, influencing the balance between dynamic and stable microtubule populations.

Mechanistically, detyrosination is carried out by tubulin carboxypeptidases, often described as complexes such as vasohibin with SVBP, though various enzymes have been implicated in detyrosinating activity. Tyrosination is catalyzed by TTL, which reattaches the tyrosine residue to detyrosinated tubulin, completing the cycle. The detyrosinated state tends to be enriched in long-lived, more stable microtubules, whereas tyrosinated tubulin is more prevalent in dynamic microtubules.

Biological significance of the cycle includes regulation of microtubule stability, interactions with motor proteins and microtubule-associated proteins, and impacts on intracellular transport, cell polarity, and neuronal development. Detyrosination can influence binding preferences of motors such as kinesin-1 and dynein, thereby affecting trafficking. The cycle interacts with other tubulin PTMs and is modulated by developmental stage, tissue type, and cellular conditions.

Clinically, alterations in the detyrosination–tyrosination balance have been observed in some neurological contexts and cancers, suggesting a role in disease processes and cellular remodeling. Overall, detyrosinationtyrosination describes a dynamic, enzyme-driven cycle that helps regulate microtubule behavior and cellular function.