C24 Sphingolipids Govern the Transbilayer Asymmetry of Cholesterol and Lateral Organization of Model and Live-Cell Plasma Membranes

K C Courtney, W Pezeshkian, R Raghupathy, C Zhang, A Darbyson, J H Ipsen, D A Ford, H Khandelia, J F Presley, X Zha

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Abstract

Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80%) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80%) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry.

Original languageEnglish
JournalCell Reports
Volume24
Issue number4
Pages (from-to)1037-1049
Number of pages13
ISSN2211-1247
DOIs
Publication statusPublished - 24. Jul 2018

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Sphingolipids
Cell membranes
Sphingomyelins
Cholesterol
Cell Membrane
Membrane Microdomains
Membranes
Unilamellar Liposomes
HeLa Cells
Free energy

Keywords

  • C24 sphingomyelin
  • FRET
  • GPI-anchored protein
  • HeLa cells
  • asymmetric membrane
  • cholesterol
  • erythrocytes
  • microdomain
  • molecular dynamics simulation
  • unilamellar vesicles

Cite this

Courtney, K C ; Pezeshkian, W ; Raghupathy, R ; Zhang, C ; Darbyson, A ; Ipsen, J H ; Ford, D A ; Khandelia, H ; Presley, J F ; Zha, X. / C24 Sphingolipids Govern the Transbilayer Asymmetry of Cholesterol and Lateral Organization of Model and Live-Cell Plasma Membranes. In: Cell Reports. 2018 ; Vol. 24, No. 4. pp. 1037-1049.
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abstract = "Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80{\%}) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80{\%}) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry.",
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C24 Sphingolipids Govern the Transbilayer Asymmetry of Cholesterol and Lateral Organization of Model and Live-Cell Plasma Membranes. / Courtney, K C; Pezeshkian, W; Raghupathy, R; Zhang, C; Darbyson, A; Ipsen, J H; Ford, D A; Khandelia, H; Presley, J F; Zha, X.

In: Cell Reports, Vol. 24, No. 4, 24.07.2018, p. 1037-1049.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - C24 Sphingolipids Govern the Transbilayer Asymmetry of Cholesterol and Lateral Organization of Model and Live-Cell Plasma Membranes

AU - Courtney, K C

AU - Pezeshkian, W

AU - Raghupathy, R

AU - Zhang, C

AU - Darbyson, A

AU - Ipsen, J H

AU - Ford, D A

AU - Khandelia, H

AU - Presley, J F

AU - Zha, X

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/7/24

Y1 - 2018/7/24

N2 - Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80%) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80%) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry.

AB - Mammalian sphingolipids, primarily with C24 or C16 acyl chains, reside in the outer leaflet of the plasma membrane. Curiously, little is known how C24 sphingolipids impact cholesterol and membrane microdomains. Here, we present evidence that C24 sphingomyelin, when placed in the outer leaflet, suppresses microdomains in giant unilamellar vesicles and also suppresses submicron domains in the plasma membrane of HeLa cells. Free energy calculations suggested that cholesterol has a preference for the inner leaflet if C24 sphingomyelin is in the outer leaflet. We indeed observe that cholesterol enriches in the inner leaflet (80%) if C24 sphingomyelin is in the outer leaflet. Similarly, cholesterol primarily resides in the cytoplasmic leaflet (80%) in the plasma membrane of human erythrocytes where C24 sphingolipids are naturally abundant in the outer leaflet. We conclude that C24 sphingomyelin uniquely interacts with cholesterol and regulates the lateral organization in asymmetric membranes, potentially by generating cholesterol asymmetry.

KW - C24 sphingomyelin

KW - FRET

KW - GPI-anchored protein

KW - HeLa cells

KW - asymmetric membrane

KW - cholesterol

KW - erythrocytes

KW - microdomain

KW - molecular dynamics simulation

KW - unilamellar vesicles

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