RT Journal Article
SR Electronic
T1 Tyrosination of α-Tubulin Controls The Initiation of Processive Dynein-Dynactin Motility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 027631
DO 10.1101/027631
A1 Richard J. McKenney
A1 Walter Huynh
A1 Ronald D. Vale
A1 Minhaj Sirajuddin
YR 2015
UL http://biorxiv.org/content/early/2015/09/25/027631.abstract
AB Post-translational modifications (PTMs) of α/β-tubulin are believed to regulate interactions with microtubule binding proteins. A well-characterized PTM involves 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 ~4-fold 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 chimeric microtubules, DDB molecules that initiated movement on tyrosinated tubulin continued moving into a region 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.