The Tubulin Detyrosination Cycle: Function and Enzymes

Microtubules are subjected to a variety of post-translational modifications (PTMs). The combination of different alpha- and beta-tubulin isoforms and PTMs are referredtoas the tubulincode. PTMs are generatedbya suite ofenzymes thought to affecttubulin-interacting proteins. OnePTMisthecyclic removalandligationof the C-terminal tyrosine of alpha-tubulin. This has been implicated in cellular processes such as mitosis, cardiomyocyte contraction, and neuronal function. Recently, vasohibins (VASHs) were identified as the first tubulin-detyrosinating enzymes, A cell-autonomous role for VASHs in regulating the cytoskeleton was unexpected due to their previous association with angiogenesis. This review discusses the functionality of the tubulin detyrosination cycle, the biology of VASHs, and highlights the emerging questions accompanying this link.