title: Regulation of microtubule motors by tubulin isotypes and post-translational modifications.
abstract: The 'tubulin-code' hypothesis proposes that different tubulin genes or post-translational modifications (PTMs), which mainly confer variation in the carboxy-terminal tail (CTT), result in unique interactions with microtubule-associated proteins for specific cellular functions. However, the inability to isolate distinct and homogeneous tubulin species has hindered biochemical testing of this hypothesis. Here, we have engineered 25 α/β-tubulin heterodimers with distinct CTTs and PTMs and tested their interactions with four different molecular motors using single-molecule assays. Our results show that tubulin isotypes and PTMs can govern motor velocity, processivity and microtubule depolymerization rates, with substantial changes conferred by even single amino acid variation. Revealing the importance and specificity of PTMs, we show that kinesin-1 motility on neuronal β-tubulin (TUBB3) is increased by polyglutamylation and that robust kinesin-2 motility requires detyrosination of α-tubulin. Our results also show that different molecular motors recognize distinctive tubulin 'signatures', which supports the premise of the tubulin-code hypothesis.
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, 600 16th Street San Francisco, California 94158, USA.
authors.forename: Minhajuddin
authors.initials: M
authors.lastname: Sirajuddin
authors.affiliation: Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard Dallas, Texas 75390, USA.
authors.forename: Luke M
authors.initials: LM
authors.lastname: Rice
authors.affiliation: Department of Cellular and Molecular Pharmacology and the Howard Hughes Medical Institute, University of California, San Francisco, 600 16th Street San Francisco, California 94158, USA.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Vale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D004398:Dyneins / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008868:Microtubule Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D016415:Sequence Alignment; D014404:Tubulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D008868:Microtubule Proteins; D020033:Protein Isoforms; D014404:Tubulin; D018698:Glutamic Acid; D014443:Tyrosine; D004398:Dyneins; D016547:Kinesins