1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
Download icon

Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics

  1. Stanley Nithiananatham
  2. Sinh Le
  3. Elbert Seto
  4. Weitao Jia
  5. Julie Leary
  6. Kevin D Corbett
  7. Jeffrey K Moore
  8. Jawdat Al-Bassam  Is a corresponding author
  1. University of California, Davis, United States
  2. University of California, San Diego, United States
  3. University of Colorado School of Medicine, United States
Research Article
  • Cited 25
  • Views 2,644
  • Annotations
Cite this article as: eLife 2015;4:e08811 doi: 10.7554/eLife.08811

Abstract

Microtubule dynamics and polarity stem from the polymerization of αß-tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate α- and β-tubulin assembly into heterodimers and maintain the soluble tubulin pool in the cytoplasm, but their physical mechanisms are unknown. Here, we reconstitute a core tubulin chaperone consisting of tubulin cofactors TBCD, TBCE and Arl2, and reveal a cage-like structure for regulating αβ-tubulin. Biochemical assays and electron microscopy structures of multiple intermediates show the sequential binding of αβ-tubulin dimer followed by tubulin cofactor TBCC onto this chaperone, forming a ternary complex in which Arl2 GTP hydrolysis is activated to alter αβ-tubulin conformation. A GTP-state locked Arl2 mutant inhibits ternary complex dissociation in vitro and causes severe defects in microtubule dynamics in vivo. Our studies suggest a revised paradigm for tubulin cofactors and Arl2 functions as a catalytic chaperone that regulates soluble αβ-tubulin assembly and maintenance to support microtubule dynamics.

Article and author information

Author details

  1. Stanley Nithiananatham

    Department of Molecular Cellular Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sinh Le

    Department of Molecular Cellular Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Elbert Seto

    Department of Molecular Cellular Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Weitao Jia

    Department of Molecular Cellular Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Julie Leary

    Department of Molecular Cellular Biology, University of California, Davis, Davis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kevin D Corbett

    Ludwig Institute for Cancer Research, University of California, San Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jeffrey K Moore

    Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jawdat Al-Bassam

    Department of Molecular Cellular Biology, University of California, Davis, Davis, United States
    For correspondence
    jawdat@ucdavis.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: May 18, 2015
  2. Accepted: July 24, 2015
  3. Accepted Manuscript published: July 24, 2015 (version 1)
  4. Version of Record published: August 18, 2015 (version 2)

Copyright

© 2015, Nithiananatham et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,644
    Page views
  • 567
    Downloads
  • 25
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    Byoungsan Choi et al.
    Research Article
    1. Biochemistry and Chemical Biology
    Masatoshi Miyamoto et al.
    Research Article