Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase

Paul Comfurius, Joan M G Senden, Roland H J Tilly, Alan J. Schroit, Edouard M. Bevers, Robert F A Zwaal

Research output: Contribution to journalArticle

222 Citations (Scopus)

Abstract

Influx of calcium in platelets and red cells produces formation of vesicles shed from the plasma membrane. The time course of the shedding process closely correlates with the ability of both cells to stimulate prothrombinase activity when used as a source of phospholipid in the prothrombinase assay. This reflects increased surface exposure of phosphatidylserine, presumably resulting from a loss in membrane asymmetry. Evidence is presented that the shed vesicles have a random phospholipid distribution, while the remnant cells show a progressive loss of membrane phospholipid asymmetry when more shedding occurs. Removal of intracellular calcium produces a decrease of procoagulant activity of the remnant cells but not of that of the shed vesicles. This is consistent with reactivation of aminophospholipid translocase activity, being first inhibited by intracellular calcium and subsequently reactivated upon calcium removal. Involvement of aminophospholipid translocase is further supported by the observation that reversibility of procoagulant activity is also dependent on metabolic ATP and reduced sulfhydryl groups. The finding that this reversibility process is not apparent in shed vesicles may be ascribed to the absence of translocase or to a lack of ATP. These data support and extend the suggestion made by Sims et al. ((1989) J. Biol. Chem. 264, 17049-17057) that membrane fusion, which is required for shedding to occur, produces transient flip-flop sites for membrane phospholipids. Furthermore, the present results indicate that scrambling of membrane phospholipids can only occur provided that aminophospholipid translocase is inactive.

Original languageEnglish (US)
Pages (from-to)153-160
Number of pages8
JournalBBA - Biomembranes
Volume1026
Issue number2
DOIs
StatePublished - Jul 24 1990

Fingerprint

Phospholipid Transfer Proteins
Cell membranes
Platelets
Phospholipids
Blood Platelets
Cells
Cell Membrane
Calcium
Membranes
Thromboplastin
Adenosine Triphosphate
Membrane Fusion
Flip flop circuits
Phosphatidylserines
Assays
Fusion reactions

Keywords

  • Aminophospholipid translocase
  • Erythrocyte
  • Flip-flop
  • Lipid asymmetry
  • Membrane shedding
  • Platelet
  • Prothrombinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase. / Comfurius, Paul; Senden, Joan M G; Tilly, Roland H J; Schroit, Alan J.; Bevers, Edouard M.; Zwaal, Robert F A.

In: BBA - Biomembranes, Vol. 1026, No. 2, 24.07.1990, p. 153-160.

Research output: Contribution to journalArticle

Comfurius, Paul ; Senden, Joan M G ; Tilly, Roland H J ; Schroit, Alan J. ; Bevers, Edouard M. ; Zwaal, Robert F A. / Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase. In: BBA - Biomembranes. 1990 ; Vol. 1026, No. 2. pp. 153-160.
@article{0533ff79c5cc444bae85174370c0ae7c,
title = "Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase",
abstract = "Influx of calcium in platelets and red cells produces formation of vesicles shed from the plasma membrane. The time course of the shedding process closely correlates with the ability of both cells to stimulate prothrombinase activity when used as a source of phospholipid in the prothrombinase assay. This reflects increased surface exposure of phosphatidylserine, presumably resulting from a loss in membrane asymmetry. Evidence is presented that the shed vesicles have a random phospholipid distribution, while the remnant cells show a progressive loss of membrane phospholipid asymmetry when more shedding occurs. Removal of intracellular calcium produces a decrease of procoagulant activity of the remnant cells but not of that of the shed vesicles. This is consistent with reactivation of aminophospholipid translocase activity, being first inhibited by intracellular calcium and subsequently reactivated upon calcium removal. Involvement of aminophospholipid translocase is further supported by the observation that reversibility of procoagulant activity is also dependent on metabolic ATP and reduced sulfhydryl groups. The finding that this reversibility process is not apparent in shed vesicles may be ascribed to the absence of translocase or to a lack of ATP. These data support and extend the suggestion made by Sims et al. ((1989) J. Biol. Chem. 264, 17049-17057) that membrane fusion, which is required for shedding to occur, produces transient flip-flop sites for membrane phospholipids. Furthermore, the present results indicate that scrambling of membrane phospholipids can only occur provided that aminophospholipid translocase is inactive.",
keywords = "Aminophospholipid translocase, Erythrocyte, Flip-flop, Lipid asymmetry, Membrane shedding, Platelet, Prothrombinase",
author = "Paul Comfurius and Senden, {Joan M G} and Tilly, {Roland H J} and Schroit, {Alan J.} and Bevers, {Edouard M.} and Zwaal, {Robert F A}",
year = "1990",
month = "7",
day = "24",
doi = "10.1016/0005-2736(90)90058-V",
language = "English (US)",
volume = "1026",
pages = "153--160",
journal = "Biochimica et Biophysica Acta - Biomembranes",
issn = "0005-2736",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase

AU - Comfurius, Paul

AU - Senden, Joan M G

AU - Tilly, Roland H J

AU - Schroit, Alan J.

AU - Bevers, Edouard M.

AU - Zwaal, Robert F A

PY - 1990/7/24

Y1 - 1990/7/24

N2 - Influx of calcium in platelets and red cells produces formation of vesicles shed from the plasma membrane. The time course of the shedding process closely correlates with the ability of both cells to stimulate prothrombinase activity when used as a source of phospholipid in the prothrombinase assay. This reflects increased surface exposure of phosphatidylserine, presumably resulting from a loss in membrane asymmetry. Evidence is presented that the shed vesicles have a random phospholipid distribution, while the remnant cells show a progressive loss of membrane phospholipid asymmetry when more shedding occurs. Removal of intracellular calcium produces a decrease of procoagulant activity of the remnant cells but not of that of the shed vesicles. This is consistent with reactivation of aminophospholipid translocase activity, being first inhibited by intracellular calcium and subsequently reactivated upon calcium removal. Involvement of aminophospholipid translocase is further supported by the observation that reversibility of procoagulant activity is also dependent on metabolic ATP and reduced sulfhydryl groups. The finding that this reversibility process is not apparent in shed vesicles may be ascribed to the absence of translocase or to a lack of ATP. These data support and extend the suggestion made by Sims et al. ((1989) J. Biol. Chem. 264, 17049-17057) that membrane fusion, which is required for shedding to occur, produces transient flip-flop sites for membrane phospholipids. Furthermore, the present results indicate that scrambling of membrane phospholipids can only occur provided that aminophospholipid translocase is inactive.

AB - Influx of calcium in platelets and red cells produces formation of vesicles shed from the plasma membrane. The time course of the shedding process closely correlates with the ability of both cells to stimulate prothrombinase activity when used as a source of phospholipid in the prothrombinase assay. This reflects increased surface exposure of phosphatidylserine, presumably resulting from a loss in membrane asymmetry. Evidence is presented that the shed vesicles have a random phospholipid distribution, while the remnant cells show a progressive loss of membrane phospholipid asymmetry when more shedding occurs. Removal of intracellular calcium produces a decrease of procoagulant activity of the remnant cells but not of that of the shed vesicles. This is consistent with reactivation of aminophospholipid translocase activity, being first inhibited by intracellular calcium and subsequently reactivated upon calcium removal. Involvement of aminophospholipid translocase is further supported by the observation that reversibility of procoagulant activity is also dependent on metabolic ATP and reduced sulfhydryl groups. The finding that this reversibility process is not apparent in shed vesicles may be ascribed to the absence of translocase or to a lack of ATP. These data support and extend the suggestion made by Sims et al. ((1989) J. Biol. Chem. 264, 17049-17057) that membrane fusion, which is required for shedding to occur, produces transient flip-flop sites for membrane phospholipids. Furthermore, the present results indicate that scrambling of membrane phospholipids can only occur provided that aminophospholipid translocase is inactive.

KW - Aminophospholipid translocase

KW - Erythrocyte

KW - Flip-flop

KW - Lipid asymmetry

KW - Membrane shedding

KW - Platelet

KW - Prothrombinase

UR - http://www.scopus.com/inward/record.url?scp=0025301753&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025301753&partnerID=8YFLogxK

U2 - 10.1016/0005-2736(90)90058-V

DO - 10.1016/0005-2736(90)90058-V

M3 - Article

C2 - 2116169

AN - SCOPUS:0025301753

VL - 1026

SP - 153

EP - 160

JO - Biochimica et Biophysica Acta - Biomembranes

JF - Biochimica et Biophysica Acta - Biomembranes

SN - 0005-2736

IS - 2

ER -