title: Tyrosination of α-tubulin controls the initiation of processive dynein-dynactin motility.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, the Howard Hughes Medical Institute University of California, San Francisco, CA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: McKenney
authors.affiliation: Department of Cellular and Molecular Pharmacology, the Howard Hughes Medical Institute University of California, San Francisco, CA, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Huynh
authors.affiliation: Department of Cellular and Molecular Pharmacology, the Howard Hughes Medical Institute University of California, San Francisco, CA, USA.
authors.forename: Ronald D
authors.identifier: 0000-0001-5742-2130
authors.initials: RD
authors.lastname: Vale
authors.affiliation: Department of Cellular and Molecular Pharmacology, the Howard Hughes Medical Institute University of California, San Francisco, CA, USA minhaj@instem.res.in.
authors.forename: Minhajuddin
authors.initials: M
authors.lastname: Sirajuddin
mesh_terms: D000072159:Dynactin Complex / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: C561542:BICD2 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D014404:Tubulin; C039520:tyrosine-tubulin; D004398:Dyneins
keywords: dynein; microtubule; post‐translational modification; tyrosination