1. Structural Biology and Molecular Biophysics
  2. Cell Biology
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Identification of a lipid scrambling domain in ANO6/TMEM16F

  1. Kuai Yu
  2. Jarred M Whitlock
  3. Kyleen Lee
  4. Eric A Ortlund
  5. Yuan Yuan Cui
  6. H Criss Hartzell  Is a corresponding author
  1. Emory University School of Medicine, United States
Research Article
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Cite this article as: eLife 2015;4:e06901 doi: 10.7554/eLife.06901

Abstract

Phospholipid scrambling (PLS) is a ubiquitous cellular mechanism involving the regulated bidirectional transport of phospholipids down their concentration gradient between membrane leaflets. ANO6/TMEM16F has been shown to be essential for Ca2+-dependent PLS, but controversy surrounds whether ANO6 is a phospholipid scramblase or an ion channel like other ANO/TMEM16 family members. Combining patch clamp recording with measurement of PLS, we show that ANO6 elicits robust Ca2+-dependent PLS coinciding with ionic currents that are explained by ionic leak during phospholipid translocation. By analyzing ANO1-ANO6 chimeric proteins, we identify a domain in ANO6 necessary for PLS and sufficient to confer this function on ANO1, which normally does not scramble. Homology modeling shows that the scramblase domain forms an unusual hydrophilic cleft that faces the lipid bilayer and may function to facilitate translocation of phospholipid between membrane leaflets. These findings provide a mechanistic framework for understanding PLS and how ANO6 functions in this process.

Article and author information

Author details

  1. Kuai Yu

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jarred M Whitlock

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kyleen Lee

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eric A Ortlund

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yuan Yuan Cui

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. H Criss Hartzell

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    For correspondence
    criss.hartzell@emory.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Randy Schekman, Howard Hughes Medical Institute, University of California, Berkeley, United States

Publication history

  1. Received: February 8, 2015
  2. Accepted: June 8, 2015
  3. Accepted Manuscript published: June 9, 2015 (version 1)
  4. Version of Record published: June 24, 2015 (version 2)

Copyright

© 2015, Yu 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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