Tyrosination of α-tubulin controls the initiation of processive dynein-dynactin motility

Richard Mckenney, Walter Huynh, Ronald D. Vale, Minhajuddin Sirajuddin

Research output: Contribution to journalArticle

66 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)1175-1185
Number of pages11
JournalEMBO Journal
Volume35
Issue number11
DOIs
StatePublished - Jun 1 2016

Keywords

  • dynein
  • microtubule
  • post-translational modification
  • tyrosination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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