detyrosinating

Detyrosination is a post-translational modification of microtubules in which a C-terminal tyrosine residue is removed from alpha-tubulin, producing detyrosinated tubulin. This modification commonly occurs on stable microtubule populations and is less prevalent on rapidly growing microtubules. Detyrosinated tubulin can persist for extended periods and can be further processed to form delta2-tubulin, a more extensively modified species.

The enzymology of detyrosination involves tubulin carboxypeptidases that cleave the C-terminal tyrosine from alpha-tubulin. The re-addition of tyrosine, a counteracting reaction, is carried out by tubulin tyrosine ligase (TTL). In human cells, a widely studied detyrosinating activity arises from a complex between vasohibins (VASH1 or VASH2) and SVBP, which functions as a tubulin carboxypeptidase. Other enzymes and regulatory factors may contribute to detyrosination in specific cell types or contexts.

Biological significance of detyrosination includes modulation of microtubule stability and dynamics, influencing interactions with motor proteins such as kinesins and dyneins, and affecting intracellular transport, cell polarity, and division. Detyrosinated microtubules are often enriched in long-lived, stable networks, notably in neurons where they are abundant in axons. The detyrosination state can impact binding of microtubule-associated proteins and can serve as a marker of microtubule age and stability. In diagnostic and research settings, antibodies targeting detyrosinated tubulin or delta2-tubulin are used to study MT turnover and related cellular processes.