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Transbilayer plasma membrane phospholipid asymmetry: Substrate specificity and protein‐protein interactions of the aminophospholipid flippase
Author(s) -
Daleke David,
Julien Michel,
Paterson Jill,
Pichika Rajeswari,
Smriti Smriti,
Zimmerman Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.932.1
Subject(s) - flippase , phospholipid scramblase , chemistry , translocase , biochemistry , lipid bilayer , phospholipid , biophysics , phosphatidylserine , microbiology and biotechnology , membrane , biology , chromosomal translocation , gene
Phospholipids in the eukaryotic plasma membrane are distributed nonrandomly across the bilayer; the choline‐containing phospholipids are enriched in the outer, and the amine‐containing phospholipids localized to the inner, monolayer. This distribution is generated and maintained by inwardly‐directed phospholipid flippases, floppase proteins that pump lipids to the outer surface and scramblases that facilitate the bi‐directional movement of lipids in activated cells. Using synthetic analogs of PS in which each of the functional groups of the lipid have been modified or removed, the plasma membrane PS flippase demonstrates a high degree of structural and stereochemical specificity for PS that is distinct from other PS binding proteins, such as protein kinase C, clotting factors, and the macrophage PS receptor, but is shared by candidate flippases from erythrocytes and some members of a new subfamily (P 4 ) of P‐type ATPases. Some of these lipid analogs are effective inhibitors of erythrocyte PS flippase activity, further defining the substrate recognition elements of the flippase. Recent evidence from other groups indicates that the activity of P 4 ‐ATPases is regulated by the CDC50 family of proteins. Using activity‐inhibiting antibodies, our studies have also revealed that the erythrocyte flippase and scramblase may interact or be activities of the same protein.