Post-translational modifications (PTMs) of α/β-tubulin are believed to regulate interactions with microtubule-binding proteins. A well-characterized PTM involves in the removal and re-ligation of the C-terminal tyrosine on α-tubulin, but the purpose of this tyrosination-detyrosination cycle remains elusive. Here, we examined the processive motility of mammalian dynein complexed with dynactin and BicD2 (DDB) on tyrosinated versus detyrosinated microtubules. Motility was decreased ~fourfold on detyrosinated microtubules, constituting the largest effect of a tubulin PTM on motor function observed to date. This preference is mediated by dynactin's microtubule-binding p150 subunit rather than dynein itself. Interestingly, on a bipartite microtubule consisting of tyrosinated and detyrosinated segments, DDB molecules that initiated movement on tyrosinated tubulin continued moving into the segment composed of detyrosinated tubulin. This result indicates that the α-tubulin tyrosine facilitates initial motor-tubulin encounters, but is not needed for subsequent motility. Our results reveal a strong effect of the C-terminal α-tubulin tyrosine on dynein-dynactin motility and suggest that the tubulin tyrosination cycle could modulate the initiation of dynein-driven motility in cells. Synopsis Post-translational modifications of tubulin can affect motor protein behavior on microtubules. This study reveals that microtubule tyrosination allows for robust initiation of mammalian dynein-dynactin processivity, but that tyrosination is dispensable once dynein is motile. Removal of alpha-tubulin carboxy-terminal tyrosine strongly decreases the interaction of the dynein-dynactin complex with microtubules. The dynein-dynactin complex has two separate microtubule binding domains. The CAP-Gly domain within the dynactin complex senses the tyrosination state of the microtubule and AIDS in the initiation of processive dynein motility. After the initiation of processive motility, the CAP-Gly interaction with the microtubule is not required for sustained dynein motility. Post-translational modifications of tubulin can affect motor protein behavior on microtubules. This study reveals that microtubule tyrosination allows for robust initiation of mammalian dynein-dynactin processivity, but that tyrosination is dispensable once dynein is motile.
- post-translational modification
ASJC Scopus subject areas
- Molecular Biology
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)