α-tubulin tail modifications regulate microtubule stability through selective effector recruitment, not changes in intrinsic polymer dynamics

Microtubules are non-covalent polymers of alpha beta-tubulin dimers. Posttranslational processing of the intrinsically disordered C-terminal alpha-tubulin tail produces detyrosinated and Delta 2-tubulin. Although these are widely employed as proxies for stable cellular microtubules, their effect (and of the alpha-tail) on microtubule dynamics remains uncharacterized. Using recombinant, engineered human tubulins, we now find that neither detyrosinated nor Delta 2-tubulin affect microtubule dynamics, while the a-tubulin tail is an inhibitor of microtubule growth. Consistent with the latter, molecular dynamics simulations show the alpha-tubulin tail transiently occluding the longitudinal microtubule polymerization interface. The marked differential in vivo stabilities of the modified microtubule subpopulations, therefore, must result exclusively from selective effector recruitment. We find that tyrosination quantitatively tunes CLIP-170 density at the growing plus end and that CLIP170 and EB1 synergize to selectively upregulate the dynamicity of tyrosinated microtubules. Modification-dependent recruitment of regulators thereby results in microtubule subpopulations with distinct dynamics, a tenet of the tubulin code hypothesis.

Automated summary

The study reveals that the stability of microtubules is influenced by the selective recruitment effect of modified microtubule subpopulations. It was found that tyrosination quantitatively tunes CLIP-170 density at the growing plus end, indicating a synergistic upregulation of dynamicity of tyrosinated microtubules by CLIP170 and EB1.