A physical mechanism of TANGO1-mediated bulky cargo export

  1. Ishier Raote  Is a corresponding author
  2. Morgan Chabanon
  3. Nikhil Walani
  4. Marino Arroyo
  5. Maria F Garcia-Parajo
  6. Vivek Malhotra  Is a corresponding author
  7. Felix Campelo  Is a corresponding author
  1. The Barcelona Institute of Science and Technology, Spain
  2. Universitat Politècnica de Catalunya-BarcelonaTech, Spain

Abstract

The endoplasmic reticulum (ER)-resident protein TANGO1 assembles into a ring around ER exit sites (ERES), and links procollagens in the ER lumen to COPII machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) in the cytoplasm (Raote et al., 2018). Here we present a theoretical approach to investigate the physical mechanisms of TANGO1 ring assembly and how COPII polymerization, membrane tension, and force facilitate the formation of a transport intermediate for procollagen export. Our results indicate that a TANGO1 ring, by acting as a linactant, stabilizes the open neck of a nascent COPII bud. Elongation of such a bud into a transport intermediate commensurate with bulky procollagens is then facilitated by two complementary mechanisms: (i) by relieving membrane tension, possibly by TANGO1-mediated fusion of retrograde ERGIC membranes; and (ii) by force application. Altogether, our theoretical approach identifies key biophysical events in TANGO1-driven procollagen export.

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. Morgan Chabanon

    ICFO - The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Castelldefels, Barcelona, Spain
    Competing interests
    No competing interests declared.
  3. Nikhil Walani

    LaCàN-Mathematical and Computational Modeling, Universitat Politècnica de Catalunya-BarcelonaTech, Barcelona, Spain
    Competing interests
    No competing interests declared.
  4. Marino Arroyo

    LaCàN-Mathematical and Computational Modeling, Universitat Politècnica de Catalunya-BarcelonaTech, Barcelona, Spain
    Competing interests
    No competing interests declared.
  5. 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.
  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
  7. Felix Campelo

    ICFO - The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Castelldefels, Barcelona, Spain
    For correspondence
    felix.campelo@icfo.eu
    Competing interests
    Felix Campelo, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0786-9548

Funding

Government of Spain (Severo Ochoa" Programme (CEX2019-000910-S)")

  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • Felix Campelo

Spanish Government (BFU2013-44188-P)

  • Ishier Raote
  • Vivek Malhotra

Spanish Government (Consolider CSD2009-00016)

  • Ishier Raote
  • Vivek Malhotra

Spanish Government (Severo Ochoa Program SEV-2012-0208)

  • Ishier Raote
  • Vivek Malhotra

Spanish Government (Maria de Maeztu MDM-2015-0502)

  • Vivek Malhotra

BIST (Ignite grant eTANGO)

  • Ishier Raote
  • Maria F Garcia-Parajo
  • Vivek Malhotra
  • Felix Campelo

Spanish Ministry of Science and Innovation (IJCI-2017-34751)

  • Ishier Raote

Spanish Ministry of Science and Innovation (RYC-2017-22227)

  • Felix Campelo

Europen Comission (CoG-681434)

  • Nikhil Walani
  • Marino Arroyo

Generalitat de Catalunya (2017-SGR-1278)

  • Marino Arroyo

ICREA (ICREA academia)

  • Marino Arroyo

Government of Spain (BFU2015-73288-JIN)

  • Maria F Garcia-Parajo
  • Felix Campelo

Spanish Government (Severo Ochoa Program,CEX2018-000797-S)

  • Marino Arroyo

State Research Agency (PID2019-106232RB-I00/ 10.13039/501100011033)

  • Morgan Chabanon
  • Felix Campelo

Government of Spain (FIS2015-63550-R)

  • Maria F Garcia-Parajo
  • Felix Campelo

Government of Spain (FIS2017-89560-R)

  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • Felix Campelo

Fundacio Privada Cellex

  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • Felix Campelo

Fundacio Privada Mir-Puig

  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • Felix Campelo

Generalitat de Catalunya (CERCA program)

  • Ishier Raote
  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • Vivek Malhotra
  • Felix Campelo

European Comission (ERC Advanced Grant (GA 788546))

  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • Felix Campelo

LaserLab 4 Europe (GA 654148)

  • Morgan Chabanon
  • Maria F Garcia-Parajo
  • 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. Jure Derganc, University of Ljubljana, Slovenia

Version history

  1. Received: June 1, 2020
  2. Accepted: November 9, 2020
  3. Accepted Manuscript published: November 10, 2020 (version 1)
  4. Version of Record published: November 30, 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.

Metrics

  • 1,789
    views
  • 282
    downloads
  • 25
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Ishier Raote
  2. Morgan Chabanon
  3. Nikhil Walani
  4. Marino Arroyo
  5. Maria F Garcia-Parajo
  6. Vivek Malhotra
  7. Felix Campelo
(2020)
A physical mechanism of TANGO1-mediated bulky cargo export
eLife 9:e59426.
https://doi.org/10.7554/eLife.59426

Share this article

https://doi.org/10.7554/eLife.59426

Further reading

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Dimitrios Vismpas, Friedrich Förster
    Insight

    Advanced cryo-EM approaches reveal surprising insights into the molecular structure that allows nascent proteins to be inserted into the membrane of the endoplasmic reticulum.

    1. Cell Biology
    2. Developmental Biology
    Corey D Holman, Alexander P Sakers ... Patrick Seale
    Research Article

    The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.