1. Biochemistry and Chemical Biology
  2. Cell Biology
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Efficient protein targeting to the inner nuclear membrane requires atlastin-dependent maintenance of ER topology

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Cite this article as: eLife 2017;6:e28202 doi: 10.7554/eLife.28202

Abstract

Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER.

Article and author information

Author details

  1. Sumit Pawar

    Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Rosemarie Ungricht

    Institute of Biochemistry, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Peter Tiefenboeck

    Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Jean-Christophe Leroux

    Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Ulrike Kutay

    Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland
    For correspondence
    ulrike.kutay@bc.biol.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8257-7465

Funding

H2020 European Research Council (ERC Advanced Grant NucEnv)

  • Sumit Pawar
  • Ulrike Kutay

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

Reviewing Editor

  1. Randy Schekman, Howard Hughes Medical Institute, University of California, Berkeley, United States

Publication history

  1. Received: April 28, 2017
  2. Accepted: August 13, 2017
  3. Accepted Manuscript published: August 14, 2017 (version 1)
  4. Version of Record published: September 6, 2017 (version 2)

Copyright

© 2017, Pawar 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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