Seipin is required for converting nascent to mature lipid droplets

  1. Huajin Wang
  2. Michel Becuwe
  3. Benjamin E Housden
  4. Chandramohan Chitraju
  5. Ashley J Porras
  6. Morven M Graham
  7. Xinran N Liu
  8. Abdou Rachid Thiam
  9. David B Savage
  10. Anil K Agarwal
  11. Abhimanyu Garg
  12. Maria-Jesus Olarte
  13. Qingqing Lin
  14. Florian Fröhlich
  15. Hans Kristian Hannibal-Bach
  16. Srigokul Upadhyayula
  17. Norbert Perrimon
  18. Tomas Kirchhausen
  19. Christer S Ejsing
  20. Tobias C Walther  Is a corresponding author
  21. Robert V Farese  Is a corresponding author
  1. Carnegie Mellon University, United States
  2. Harvard T. H. Chan School of Public Health, United States
  3. Harvard Medical School, United States
  4. Yale School of Medicine, United States
  5. PSL Research University, France
  6. The University of Cambridge Metabolic Research Laboratories, United Kingdom
  7. UT Southwestern Medical Center, United States
  8. University of Southern Denmark, Denmark

Abstract

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.

Article and author information

Author details

  1. Huajin Wang

    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Michel Becuwe

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Benjamin E Housden

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Chandramohan Chitraju

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ashley J Porras

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Morven M Graham

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Xinran N Liu

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Abdou Rachid Thiam

    Laboratoire de Physique Statistique, École Normale Supérieure, PSL Research University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. David B Savage

    Wellcome Trust-MRC Institute of Metabolic Science, The University of Cambridge Metabolic Research Laboratories, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Anil K Agarwal

    Division of Nutrition and Metabolic Diseases, UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Abhimanyu Garg

    Division of Nutrition and Metabolic Diseases, UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Maria-Jesus Olarte

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Qingqing Lin

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Florian Fröhlich

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Hans Kristian Hannibal-Bach

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  16. Srigokul Upadhyayula

    Departments of Cell Biology and Pediatrics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Norbert Perrimon

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Tomas Kirchhausen

    Departments of Cell Biology and Pediatrics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Christer S Ejsing

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  20. Tobias C Walther

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    For correspondence
    twalther@hsph.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
  21. Robert V Farese

    Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, United States
    For correspondence
    robert@hsph.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8103-2239

Funding

National Institutes of Health (GM099844, GM097194, GM-075252)

  • Tomas Kirchhausen
  • Tobias C Walther
  • Robert V Farese

Howard Hughes Medical Institute

  • Norbert Perrimon
  • Tobias C Walther

G Harold and Leila Y. Mathers Foundation

  • Tobias C Walther

Villum Fonden (VKR023439)

  • Christer S Ejsing

Danish Council for Strategic Research (11-116196)

  • Christer S Ejsing

Wellcome Trust (WT107064)

  • David B Savage

Cambridge NIHR BRC

  • David B Savage

Biogen

  • Tomas Kirchhausen

Canadian Institutes of Health Research (Fellowship Award)

  • Huajin Wang

European Molecular Biology Organization (Longterm Fellowship EMBOLFT355)

  • Michel Becuwe

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

Reviewing Editor

  1. Stephen G Young, University of California, Los Angeles, United States

Version history

  1. Received: April 1, 2016
  2. Accepted: August 25, 2016
  3. Accepted Manuscript published: August 26, 2016 (version 1)
  4. Version of Record published: September 23, 2016 (version 2)

Copyright

© 2016, Wang 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. Huajin Wang
  2. Michel Becuwe
  3. Benjamin E Housden
  4. Chandramohan Chitraju
  5. Ashley J Porras
  6. Morven M Graham
  7. Xinran N Liu
  8. Abdou Rachid Thiam
  9. David B Savage
  10. Anil K Agarwal
  11. Abhimanyu Garg
  12. Maria-Jesus Olarte
  13. Qingqing Lin
  14. Florian Fröhlich
  15. Hans Kristian Hannibal-Bach
  16. Srigokul Upadhyayula
  17. Norbert Perrimon
  18. Tomas Kirchhausen
  19. Christer S Ejsing
  20. Tobias C Walther
  21. Robert V Farese
(2016)
Seipin is required for converting nascent to mature lipid droplets
eLife 5:e16582.
https://doi.org/10.7554/eLife.16582

Share this article

https://doi.org/10.7554/eLife.16582

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