Regulated externalization of phosphatidylserine at the cell surface: implications for apoptosis.
The regulated loss of plasma membrane phosphatidylserine (PS) asymmetry is critical to many biological processes. In particular, the appearance of PS at the cell surface, a hallmark of apoptosis, prepares the dying cell for engulfment and elimination by phagocytes. While it is well established that PS externalization is regulated by activation of a calcium-dependent phospholipid scramblase activity in concert with inactivation of the aminophospholipid translocase, there is no evidence indicating that these processes are triggered and regulated by apoptotic regulatory mechanisms. Using a novel model system, we show that PS externalization is inducible, reversible, and independent of cytochrome c release, caspase activation, and DNA fragmentation. Additional evidence is presented indicating that the outward movement of plasma membrane PS requires sustained elevation in cytosolic Ca2+ in concert with inactivation of the aminophospholipid translocase and is inhibited by calcium channel blockers.
Balasubramanian
Krishnakumar
K
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Mirnikjoo
Banafsheh
B
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
Schroit
Alan J
AJ
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030. Electronic address: aschroit@mdanderson.org.
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D010586:Phagocytes / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism
D008055:Lipids; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D045304:Cytochromes c; D002118:Calcium