TANGO1 builds a machine for collagen export by recruiting and spatially organizing COPII, tethers and membranes

  1. Ishier Raote
  2. Maria Ortega-Bellido
  3. António J M Santos
  4. Ombretta Foresti
  5. Chong Zhang
  6. Maria F Garcia-Parajo
  7. Felix Campelo
  8. Vivek Malhotra  Is a corresponding author
  1. The Barcelona Institute of Science and Technology, Spain
  2. Universitat Pompeu Fabra, Spain

Abstract

Collagen export from the endoplasmic reticulum (ER) requires TANGO1, COPII coats, and retrograde fusion of ERGIC membranes. How do these components come together to produce a transport carrier commensurate with the bulky cargo collagen? TANGO1 is known to form a ring that corrals COPII coats and we show here how this ring or fence is assembled. Our data reveal that a TANGO1 ring is organized by its radial interaction with COPII, and lateral interactions with cTAGE5, TANGO1-short or itself. Of particular interest is the finding that TANGO1 recruits ERGIC membranes for collagen export via the NRZ (NBAS/RINT1/ZW10) tether complex. Therefore, TANGO1 couples retrograde membrane flow to anterograde cargo transport. Without the NRZ complex, the TANGO1 ring does not assemble, suggesting its role in nucleating or stabilising of this process. Thus, coordinated capture of COPII coats, cTAGE5, TANGO1-short, and tethers by TANGO1 assembles a collagen export machine at the ER.

Article and author information

Author details

  1. Ishier Raote

    Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5898-4896
  2. Maria Ortega-Bellido

    Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
  3. António J M Santos

    Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
  4. Ombretta Foresti

    Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6878-0395
  5. Chong Zhang

    Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    No competing interests declared.
  6. Maria F Garcia-Parajo

    ICFO - The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
  7. Felix Campelo

    ICFO - The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0786-9548
  8. 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 (BFU2013-44188-P)

  • Vivek Malhotra

AEI/FEDER, UE

  • Maria F Garcia-Parajo

Human Frontier Science Program (GA RGP0027/2012)

  • Maria F Garcia-Parajo

Cordis (EC FP7-NANO-VISTA (GA 288263)

  • Maria F Garcia-Parajo

LaserLab 4 Europe (GA 654148)

  • Maria F Garcia-Parajo

Ministerio de Economía y Competitividad (CSD2009-00016)

  • Vivek Malhotra

Barcelona Institute of Science and Technology (BIST-IGNITE-eTANGO)

  • Ishier Raote
  • Felix Campelo
  • Vivek Malhotra

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

  • Vivek Malhotra

Ministerio de Economía y Competitividad (SEV-2015-240522)

  • Vivek Malhotra

Ministerio de Economía y Competitividad (FIS2014-56107-R)

  • Maria F Garcia-Parajo

Ministerio de Economía y Competitividad (MDM-2015-0502)

  • Vivek Malhotra

Ministerio de Economía y Competitividad (BFU2015-73288-JIN)

  • Maria F Garcia-Parajo

Fundacion Privada Cellex

  • Maria F Garcia-Parajo

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

Reviewing Editor

  1. Suzanne R Pfeffer, Stanford University School of Medicine, United States

Publication history

  1. Received: October 12, 2017
  2. Accepted: March 2, 2018
  3. Accepted Manuscript published: March 7, 2018 (version 1)
  4. Version of Record published: March 14, 2018 (version 2)

Copyright

© 2018, 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. Maria Ortega-Bellido
  3. António J M Santos
  4. Ombretta Foresti
  5. Chong Zhang
  6. Maria F Garcia-Parajo
  7. Felix Campelo
  8. Vivek Malhotra
(2018)
TANGO1 builds a machine for collagen export by recruiting and spatially organizing COPII, tethers and membranes
eLife 7:e32723.
https://doi.org/10.7554/eLife.32723

Further reading

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    Ishier Raote et al.
    Research Advance Updated

    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.

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