The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix

  1. David Barneda
  2. Joan Planas-Iglesias
  3. Maria L Gaspar
  4. Dariush Mohammadyani
  5. Sunil Prasannan
  6. Dirk Dormann
  7. Gil-Soo Han
  8. Stephen A Jesch
  9. George M Carman
  10. Valerian Kagan
  11. Malcolm G Parker
  12. Nicholas T Ktistakis
  13. Ann M Dixon
  14. Judith Klein-Seetharaman
  15. Susan Henry
  16. Mark Christian  Is a corresponding author
  1. Imperial College London, United Kingdom
  2. University of Warwick, United Kingdom
  3. Cornell University, United States
  4. University of Pittsburgh, United States
  5. Imperial College London, United States
  6. Rutgers University, United States
  7. Babraham Institute, United Kingdom

Abstract

Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD-LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.

Article and author information

Author details

  1. David Barneda

    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Joan Planas-Iglesias

    Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Maria L Gaspar

    Department of Molecular Biology and Genetics, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Dariush Mohammadyani

    Department of Bioengineering, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sunil Prasannan

    Department of Chemistry, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Dirk Dormann

    Microscopy Facility, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Gil-Soo Han

    Microscopy Facility, MRC Clinical Sciences Centre, Imperial College London, London, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Stephen A Jesch

    Department of Molecular Biology and Genetics, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. George M Carman

    Department of Food Science, Rutgers Center for Lipid Research, Rutgers University, New Brunswick, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Valerian Kagan

    Department of Bioengineering, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Malcolm G Parker

    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Nicholas T Ktistakis

    Signalling Programme, Babraham Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Ann M Dixon

    Department of Chemistry, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Judith Klein-Seetharaman

    Warwick Medical School, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Susan Henry

    Department of Molecular Biology and Genetics, Cornell University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Mark Christian

    Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
    For correspondence
    m.christian@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

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

Version history

  1. Received: March 13, 2015
  2. Accepted: November 25, 2015
  3. Accepted Manuscript published: November 26, 2015 (version 1)
  4. Accepted Manuscript updated: December 10, 2015 (version 2)
  5. Version of Record published: February 3, 2016 (version 3)

Copyright

© 2015, Barneda 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

  • 4,332
    views
  • 1,163
    downloads
  • 96
    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. David Barneda
  2. Joan Planas-Iglesias
  3. Maria L Gaspar
  4. Dariush Mohammadyani
  5. Sunil Prasannan
  6. Dirk Dormann
  7. Gil-Soo Han
  8. Stephen A Jesch
  9. George M Carman
  10. Valerian Kagan
  11. Malcolm G Parker
  12. Nicholas T Ktistakis
  13. Ann M Dixon
  14. Judith Klein-Seetharaman
  15. Susan Henry
  16. Mark Christian
(2015)
The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix
eLife 4:e07485.
https://doi.org/10.7554/eLife.07485

Share this article

https://doi.org/10.7554/eLife.07485

Further reading

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Shun Kai Yang, Shintaroh Kubo ... Khanh Huy Bui
    Research Article

    Acetylation of α-tubulin at the lysine 40 residue (αK40) by αTAT1/MEC-17 acetyltransferase modulates microtubule properties and occurs in most eukaryotic cells. Previous literatures suggest that acetylated microtubules are more stable and damage resistant. αK40 acetylation is the only known microtubule luminal post-translational modification site. The luminal location suggests that the modification tunes the lateral interaction of protofilaments inside the microtubule. In this study, we examined the effect of tubulin acetylation on the doublet microtubule (DMT) in the cilia of Tetrahymena thermophila using a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry. We found that αK40 acetylation exerts a small-scale effect on the DMT structure and stability by influencing the lateral rotational angle. In addition, comparative mass spectrometry revealed a link between αK40 acetylation and phosphorylation in cilia.

    1. Structural Biology and Molecular Biophysics
    Sebastian Jojoa-Cruz, Adrienne E Dubin ... Andrew B Ward
    Research Advance

    The dimeric two-pore OSCA/TMEM63 family has recently been identified as mechanically activated ion channels. Previously, based on the unique features of the structure of OSCA1.2, we postulated the potential involvement of several structural elements in sensing membrane tension (Jojoa-Cruz et al., 2018). Interestingly, while OSCA1, 2, and 3 clades are activated by membrane stretch in cell-attached patches (i.e. they are stretch-activated channels), they differ in their ability to transduce membrane deformation induced by a blunt probe (poking). Here, in an effort to understand the domains contributing to mechanical signal transduction, we used cryo-electron microscopy to solve the structure of Arabidopsis thaliana (At) OSCA3.1, which, unlike AtOSCA1.2, only produced stretch- but not poke-activated currents in our initial characterization (Murthy et al., 2018). Mutagenesis and electrophysiological assessment of conserved and divergent putative mechanosensitive features of OSCA1.2 reveal a selective disruption of the macroscopic currents elicited by poking without considerable effects on stretch-activated currents (SAC). Our results support the involvement of the amphipathic helix and lipid-interacting residues in the membrane fenestration in the response to poking. Our findings position these two structural elements as potential sources of functional diversity within the family.