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Identification of a lipid scrambling domain in ANO6/TMEM16F.

Kuai Yu | Jarred M Whitlock | Kyleen Lee | Eric A Ortlund | Yuan Yuan Cui | H Criss Hartzell
eLife | 2015

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 Ca(2+)-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 Ca(2+)-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.

Pubmed ID: 26057829

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: GM60448-12
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008367
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR067786
  • Agency: NEI NIH HHS, United States
    Id: EY114852-11
  • Agency: NIGMS NIH HHS, United States
    Id: 5T32GM008367-25
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM060448
  • Agency: NEI NIH HHS, United States
    Id: R01 EY014852
  • Agency: NINDS NIH HHS, United States
    Id: P30 NS055077

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