detyrosination

Detyrosination is a post-translational modification of tubulin that involves the enzymatic removal of the C-terminal tyrosine residue from alpha-tubulin. This reaction generates a form of tubulin known as Glu-tubulin at the C-terminus, which can be re-tyrosinated by tubulin tyrosine ligase (TTL) to restore the original tyrosine. The detyrosination-retyrosination cycle is a dynamic process that contributes to the regulation of microtubule properties and function.

Enzymes and mechanism have evolved to support this cycle. Detyrosination is carried out by a tubulin detyrosinating enzyme, historically referred to as a tubulin tyrosine carboxypeptidase (TTCP). In many animal cells, the detyrosinating activity is carried out by a complex of vasohibins (VASH1 and VASH2) with SVBP (small vasohibin-binding protein), which acts as an active detyrosinating enzyme for alpha-tubulin. TTL, the tubulin tyrosine ligase, then catalyzes the re-addition of tyrosine to regenerate Tyr-tubulin.

Biological significance and distribution are closely linked to microtubule stability. Detyrosinated tubulin (Glu-tubulin) is enriched in long-lived, more stable microtubules and plays a role in the interaction with motor proteins such as kinesin and dynein, as well as various microtubule-associated proteins. The detyrosination status influences microtubule dynamics and cargo transport, with notable relevance in neurons and during development. Aberrant detyrosination levels have been investigated in aging and certain diseases, including cancer.

Detection methods often rely on antibodies that recognize detyrosinated or Glu-tubulin, which serve as markers of stable microtubule populations. Detyrosination is one component of the broader tubulin code, which also includes other modifications such as polyglutamylation and acetylation, and it can interact with these marks to modulate microtubule behavior.