Scott syndrome, a bleeding disorder caused by defective scrambling of membrane phospholipids.
Normal quescent cells maintain membrane lipid asymmetry by ATP-dependent membrane lipid transporters, which shuttle different phospholipids from one leaflet to the other against their respective concentration gradients. When cells are challenged, membrane lipid asymmetry can be perturbed resulting in exposure of phosphatidylserine [PS] at the outer cell surface. Translocation of PS from the inner to outer membrane leaflet of activated blood platelets and platelet-derived microvesicles provides a catalytic surface for interacting coagulation factors. This process is dramatically impaired in Scott syndrome, a rare congenital bleeding disorder, underscoring the indispensible role of PS in hemostasis. This also testifies to a defect of a protein-catalyzed scrambling of membrane phospholipids. The Scott phenotype is not restricted to platelets, but can be demonstrated in other blood cells as well. The functional aberrations observed in Scott syndrome have increased our understanding of transmembrane lipid movements, and may help to identify the molecular elements that promote the collapse of phospholipid asymmetry during cell activation and apoptosis.
Zwaal
Robert F A
RF
Cardiovascular Research Institute Maastricht, and Department of Biochemistry, Maastricht University, PO Box 616, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands. rfa.zwaal@bioch.unimaas.nl
Comfurius
Paul
P
Bevers
Edouard M
EM
D001778:Blood Coagulation Disorders / Q000378:metabolism*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism* / Q000502:physiology; D010743:Phospholipids / Q000378:metabolism* / Q000502:physiology; D013577:Syndrome
D008563:Membrane Lipids; D010743:Phospholipids