Phospholipid scramblase activation pathways in lymphocytes.
In erythrocytes and platelets, activation of a nonspecific lipid flipsite termed the scramblase allows rapid, bidirectional transbilayer movement of all types of phospholipids. When applied to lymphoid cells, scramblase assays reveal a similar activity, with scrambling rates intermediate between those seen in platelets and erythrocytes. Scrambling activity initiated in lymphoid cells by elevation of intracellular Ca(2+) proceeds after a lag not noted in platelets or erythrocytes. The rates of transbilayer movement of phosphatidylserine and phosphatidylcholine analogues are similar whether the scramblase is activated by elevated internal Ca(2+) or by apoptosis. Elevation of internal Ca(2+) levels in apoptotic cells does not result in an additive increase in the rate of lipid movement. In lymphoid cells from a patient with Scott syndrome, scramblase cannot be activated by Ca(2+), but is induced normally during apoptosis. These findings suggest that Ca(2+) and apoptosis operate through different pathways to activate the same scramblase.
Williamson
P
P
Department of Biology, Amherst College, Amherst, Massachusetts 01002, USA.
Christie
A
A
Kohlin
T
T
Schlegel
R A
RA
Comfurius
P
P
Harmsma
M
M
Zwaal
R F
RF
Bevers
E M
EM
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000201:enzymology / Q000473:pathology; D001778:Blood Coagulation Disorders / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D004789:Enzyme Activation / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas; D019169:Jurkat Cells; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013577:Syndrome
C078632:1-acyl-2-(12-((7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)dodecanoyl)phosphatidylcholine; D002352:Carrier Proteins; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C063384:1-oleoyl-2-((N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino)caproyl)phosphatidylserine; D009327:4-Chloro-7-nitrobenzofurazan; D002118:Calcium