Phospholipid-flipping activity of P4-ATPase drives membrane curvature

EMBO J. 2018 May 2;37(9):e97705. doi: 10.15252/embj.201797705. Epub 2018 Mar 29.

Abstract

P4-ATPases are phospholipid flippases that translocate phospholipids from the exoplasmic/luminal to the cytoplasmic leaflet of biological membranes. All P4-ATPases in yeast and some in other organisms are required for membrane trafficking; therefore, changes in the transbilayer lipid composition induced by flippases are thought to be crucial for membrane deformation. However, it is poorly understood whether the phospholipid-flipping activity of P4-ATPases can promote membrane deformation. In this study, we assessed membrane deformation induced by flippase activity via monitoring the extent of membrane tubulation using a system that allows inducible recruitment of Bin/amphiphysin/Rvs (BAR) domains to the plasma membrane (PM). Enhanced phosphatidylcholine-flippase activity at the PM due to expression of ATP10A, a member of the P4-ATPase family, promoted membrane tubulation upon recruitment of BAR domains to the PM This is the important evidence that changes in the transbilayer lipid composition induced by P4-ATPases can deform biological membranes.

Keywords: BAR domain; curvature; flippase; lipid; plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Cell Membrane / enzymology*
  • Cell Membrane / genetics
  • HeLa Cells
  • Humans
  • Lipid Bilayers / metabolism*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Phosphatidylcholines / genetics
  • Phosphatidylcholines / metabolism*

Substances

  • Lipid Bilayers
  • Membrane Transport Proteins
  • Phosphatidylcholines
  • Adenosine Triphosphatases
  • ATP10A protein, human