TANGO1 membrane helices create a lipid diffusion barrier at curved membranes

  1. Ishier Raote  Is a corresponding author
  2. Andreas M Ernst
  3. Felix Campelo
  4. James E Rothman
  5. Frederic Pincet  Is a corresponding author
  6. Vivek Malhotra  Is a corresponding author
  1. The Barcelona Institute of Science and Technology, Spain
  2. Yale School of Medicine, United States
  3. ICFO - The Institute of Photonic Sciences, Spain
  4. Ecole Normal Superieure, France

Abstract

We have previously shown TANGO1 organises membranes at the interface of the endoplasmic reticulum (ER) and ERGIC/Golgi (Raote et al., 2018). TANGO1 corrals retrograde membranes at ER exit sites to create an export conduit. Here the retrograde membrane is, in itself, an anterograde carrier. This mode of forward transport necessitates a mechanism to prevent membrane mixing between ER and the retrograde membrane. TANGO1 has an unusual membrane helix organisation, composed of one membrane-spanning helix (TM) and another that penetrates the inner leaflet (IM). We have reconstituted these membrane helices in model membranes and shown that TM and IM together reduce the flow of lipids at a region of defined shape. We have also shown that the helices align TANGO1 around an ER exit site. We suggest this is a mechanism to prevent membrane mixing during TANGO1-mediated transfer of bulky secretory cargos from the ER to the ERGIC/Golgi via a tunnel.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Ishier Raote

    Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
    For correspondence
    ishier.raote@crg.eu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5898-4896
  2. Andreas M Ernst

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
  3. Felix Campelo

    ICFO - The Institute of Photonic Sciences, Barcelona, Spain
    Competing interests
    Felix Campelo, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0786-9548
  4. James E Rothman

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8653-8650
  5. Frederic Pincet

    Laboratoire de Physique de l'Ecole Normale Supérieure, Ecole Normal Superieure, Paris, France
    For correspondence
    frederic.pincet@ens.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4243-2157
  6. Vivek Malhotra

    Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
    For correspondence
    vivek.malhotra@crg.eu
    Competing interests
    Vivek Malhotra, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6198-7943

Funding

Ministerio de Economía y Competitividad (SEV-2012-0208)

  • Ishier Raote
  • Vivek Malhotra

Generalitat de Catalunya (CERCA)

  • Felix Campelo

Ministerio de Economía y Competitividad (BFU2013-44188-P)

  • Ishier Raote
  • Vivek Malhotra

Ministerio de Economía y Competitividad (CSD2009-00016)

  • Ishier Raote
  • Vivek Malhotra

Ministerio de Economía y Competitividad (IJCI-2017-34751)

  • Ishier Raote

National Institutes of Health (R35 GM118084)

  • James E Rothman

Ministerio de Economía y Competitividad (SEV-2015-0522)

  • Felix Campelo

Ministerio de Economía y Competitividad (RYC-2017-22227)

  • Felix Campelo

Fundacio Privada Cellex

  • Felix Campelo

Fundacio Privada Mir-Puig

  • Felix Campelo

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

Reviewing Editor

  1. Adam Linstedt, Carnegie Mellon University, United States

Publication history

  1. Received: April 15, 2020
  2. Accepted: May 21, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Version of Record published: June 2, 2020 (version 2)

Copyright

© 2020, Raote 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. Ishier Raote
  2. Andreas M Ernst
  3. Felix Campelo
  4. James E Rothman
  5. Frederic Pincet
  6. Vivek Malhotra
(2020)
TANGO1 membrane helices create a lipid diffusion barrier at curved membranes
eLife 9:e57822.
https://doi.org/10.7554/eLife.57822

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