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PMID: 24633327 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Regulation of microtubule motors by tubulin isotypes and post-translational modifications.

Nature cell biology ·Vol. 16 ·No. 4 ·2014-04-00 ·Pages 335-44

Sirajuddin M, Rice LM, Vale RD

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.

MeSH Terms
Amino Acid Sequence Animals Cricetinae Dyneins/metabolism Glutamic Acid/chemistry Humans Kinesins/metabolism Microtubule Proteins/metabolism Molecular Sequence Data Protein Isoforms/genetics,metabolism Protein Processing, Post-Translational/genetics Sequence Alignment Tubulin/chemistry,genetics,metabolism Tyrosine/chemistry
Chemicals
Microtubule Proteins Protein Isoforms Tubulin Glutamic Acid Tyrosine Dyneins Kinesins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sirajuddin Minhajuddin
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.
Rice Luke M
Departments of Biophysics and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard Dallas, Texas 75390, USA.
Vale Ronald D
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.
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2920
Published
2014-04-00
Epub
2014-00-16
Pages
335-44
Language
English
Region
England
NLM ID
100890575
PMCID
PMC4117587
Subset
IM
Grants
NIGMS NIH HHS · R37 GM038499 · United States
Howard Hughes Medical Institute · United States
PHS HHS · 38499 · United States
Corrections
CommentIn
PMID: 24691257
External Links
PubMed source DOI: 10.1038/ncb2920 PMC Full Text View journal details
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