Lissencephaly-1 is a context-dependent regulator of the human dynein complex

  1. Janina Baumbach
  2. Andal Murthy
  3. Mark A McClintock
  4. Carly I Dix
  5. Ruta Zalyte
  6. Ha Thi Hoang
  7. Simon L Bullock  Is a corresponding author
  1. MRC Laboratory of Molecular Biology, United Kingdom

Abstract

The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein and its accessory complex dynactin with dynamic microtubule plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein-1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus end-directed human dynein complexes with these sites. LIS1 promotes dynactin-dependent tracking of dynein on both growing and shrinking plus ends. LIS1 also increases the frequency and velocity of processive dynein movements that are activated by complex formation with dynactin and a cargo adaptor. This stimulatory effect of LIS1 contrasts sharply with its documented ability to inhibit the activity of isolated dyneins. Collectively, our findings shed light on how mammalian dynein complexes associate with dynamic microtubules and help clarify how LIS1 promotes the plus end localisation and cargo transport functions of dynein in vivo.

Article and author information

Author details

  1. Janina Baumbach

    Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Andal Murthy

    Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Mark A McClintock

    Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Carly I Dix

    Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Ruta Zalyte

    Division of Structural Studies, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Ha Thi Hoang

    Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Simon L Bullock

    Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    For correspondence
    sbullock@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9491-4548

Funding

Medical Research Council (MC_U105178790)

  • Simon L Bullock

Deutsche Forschungsgemeinschaft (BA 5802/1-1)

  • Janina Baumbach

Boehringer Ingelheim Fonds

  • Ha Thi Hoang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: September 22, 2016
  2. Accepted: April 11, 2017
  3. Accepted Manuscript published: April 13, 2017 (version 1)
  4. Version of Record published: May 2, 2017 (version 2)

Copyright

© 2017, Baumbach 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.

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  1. Janina Baumbach
  2. Andal Murthy
  3. Mark A McClintock
  4. Carly I Dix
  5. Ruta Zalyte
  6. Ha Thi Hoang
  7. Simon L Bullock
(2017)
Lissencephaly-1 is a context-dependent regulator of the human dynein complex
eLife 6:e21768.
https://doi.org/10.7554/eLife.21768

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