Impaired redistribution of aminophospholipids with distinctive cell shape change during Ca²⁺‐induced activation of platelets from a patient with Scott syndrome

Abstract

Summary.We have investigated phospholipid redistribution, membrane vesicle shedding, shape change, and granule release following A23187 activation of platelets from a patient with Scott syndrome, characterized by impaired transmembrane migration of phosphatidylserine (PS) accompanied by haemorrhagic complications, and two of her children. Electron spin resonance spectroscopy measurement of phospholipids redistribution showed that the internalization of PS was unaffected by the disorder but, after activation, PS exposure was significantly reduced in platelets from the homozygous-type patient. Vesicle shedding was also reduced in these platelets. However, the slow redistribution of phosphatidylcholine was similar to that observed in normal platelets. When treated with calpeptin, platelets from the homozygous-type patient, unlike normal or heterozygous Scott syndrome platelets, showed a smoothly rounded shape without filopods after activation. Following A23187 activation of normal platelets, filopod formation was consecutive to the re-exposition of aminophospholipids on the outer leaflet of the plasma membrane, and the existence of a floppase (outward aminoPLs translocase) has been suggested. In homozygous Scott syndrome platelets the deficiency in PS re-exposition, the absence of filopod formation, and low vesicle shedding are correlated with each other, and argue in favour of a disruption of the proposed floppase activity.

Mechanical constraint imposed on plasma membrane through transverse phospholipid imbalance induces reversible actin polymerization via phosphoinositide 3-kinase activation

“…1d-e). As expected (Bettache et al, 1998), Ca 2+ -ionophore activation of platelets pre-treated with calpeptin induced changes in shape with filopodia extension (Fig. 1f).…”

“…This filopodia formation seems to be related to an excess of PL in the outer leaflet of the plasma membrane and to cytoskeleton reorganization induced by actin polymerization. In Scott syndrome, where PS exposure is significantly reduced during platelet activation, no filopodia are formed (Bettache et al, 1998). This indicates that filopodia formation tightly correlates with the specific outflux of aminophospholipids resulting in an excess of PL in the outer leaflet of plasma membrane of activated platelets.…”

Phosphatidylserine, a death knell

“…At present, regulation of these processes is not well understood in either system, but a natural mutation which prevents activation of the scramblase is manifest in Scott syndrome. 136,137 Since the translocase is regulated normally in the cells of Scott syndrome patients, 137 it and the scramblase appear to be regulated independently of one another. The scramblase in normal platelets is activated by a Ca 2+ -mediated signaling pathway which fails to activate the scramblase in Scott platelets.…”

Transmembrane Dynamics of Lipids

“…A rare but severe disease, called " Scott syndrome, " is characterized by the absence of PS redistribution upon calcium entry and has been investigated by R. Zwaal ' s group in The Netherlands [32] and by J. -M. Freyssinet and collaborators [33] in France.…”