Journal
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
Volume 466, Issue 7, Pages 1227-1240Publisher
SPRINGER
DOI: 10.1007/s00424-013-1363-4
Keywords
Flippase; Lipid asymmetry; P-type pump; CDC50 protein; Vesicle biogenesis; Importer
Categories
Funding
- UNIK research initiative of the Danish Ministry of Science, Technology and Innovation through the Center for Synthetic Biology at the University of Copenhagen
- Danish National Research Foundation through the PUMPKIN Center of Excellence [DNRF85]
- Danish Council for Independent Research \ Natural Sciences (FNU) [10-083406]
- Lundbeck Foundation
- Deutsche Forschungsgemeinschaft
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Cellular membranes, notably eukaryotic plasma membranes, are equipped with special proteins that actively translocate lipids from one leaflet to the other and thereby help generate membrane lipid asymmetry. Among these ATP-driven transporters, the P4 subfamily of P-type ATPases (P4-ATPases) comprises lipid flippases that catalyze the translocation of phospholipids from the exoplasmic to the cytosolic leaflet of cell membranes. While initially characterized as aminophospholipid translocases, recent studies of individual P4-ATPase family members from fungi, plants, and animals show that P4-ATPases differ in their substrate specificities and mediate transport of a broader range of lipid substrates, including lysophospholipids and synthetic alkylphospholipids. At the same time, the cellular processes known to be directly or indirectly affected by this class of transporters have expanded to include the regulation of membrane traffic, cytoskeletal dynamics, cell division, lipid metabolism, and lipid signaling. In this review, we will summarize the basic features of P4-ATPases and the physiological implications of their lipid transport activity in the cell.
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