Inner workings and biological impact of phospholipid flippases.
The plasma membrane, trans-Golgi network and endosomal system of eukaryotic cells are populated with flippases that hydrolyze ATP to help establish asymmetric phospholipid distributions across the bilayer. Upholding phospholipid asymmetry is vital to a host of cellular processes, including membrane homeostasis, vesicle biogenesis, cell signaling, morphogenesis and migration. Consequently, defining the identity of flippases and their biological impact has been the subject of intense investigations. Recent work has revealed a remarkable degree of kinship between flippases and cation pumps. In this Commentary, we review emerging insights into how flippases work, how their activity is controlled according to cellular demands, and how disrupting flippase activity causes system failure of membrane function, culminating in membrane trafficking defects, aberrant signaling and disease.
Department of Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 Utrecht, The Netherlands Molecular Cell Biology Division, University of Osnabrück, 49076 Osnabrück, Germany.
Radhakrishnan
R
Panatala
Department of Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 Utrecht, The Netherlands.
Hanka
H
Hennrich
Department of Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 Utrecht, The Netherlands Molecular Cell Biology Division, University of Osnabrück, 49076 Osnabrück, Germany holthuis@uos.de.
Joost C M
JC
Holthuis
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism
D049294:Phospholipid Transfer Proteins; D010743:Phospholipids
Flippase; Golgi complex; Lipid asymmetry; P-type ATPase; Phosphatidylserine; Vesicular transport