PMID- 34843684
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220402
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 63
IP  - 1
DP  - 2022 Jan
TI  - Loss of plasma membrane lipid asymmetry can induce ordered domain (raft) 
      formation.
PG  - 100155
LID - S0022-2275(21)00138-3 [pii]
LID - 10.1016/j.jlr.2021.100155 [doi]
LID - 100155
AB  - In some cases, lipids in one leaflet of an asymmetric artificial lipid vesicle 
      suppress the formation of ordered lipid domains (rafts) in the opposing leaflet. 
      Whether this occurs in natural membranes is unknown. Here, we investigated this 
      issue using plasma membrane vesicles (PMVs) from rat leukemia RBL-2H3 cells. 
      Membrane domain formation and order was assessed by fluorescence resonance energy 
      transfer and fluorescence anisotropy. We found that ordered domains in PMVs 
      prepared from cells by N-ethyl maleimide (NEM) treatment formed up to  approximately 37 degrees C, 
      whereas ordered domains in symmetric vesicles formed from the extracted PMV 
      lipids were stable up to 55 degrees C, indicating the stability of ordered domains was 
      substantially decreased in intact PMVs. This behavior paralleled lesser ordered 
      domain stability in artificial asymmetric lipid vesicles relative to the 
      corresponding symmetric vesicles, suggesting intact PMVs exhibit some degree of 
      lipid asymmetry. This was supported by phosphatidylserine mislocalization on PMV 
      outer leaflets as judged by annexin binding, which indicated NEM-induced PMVs are 
      much more asymmetric than PMVs formed by dithiothreitol/paraformaldehyde 
      treatment. Destroying asymmetry by reconstitution of PMVs using detergent 
      dilution also showed stabilization of domain formation, even though membrane 
      proteins remained associated with reconstituted vesicles. Similar domain 
      stabilization was observed in artificial asymmetric lipid vesicles after 
      destroying asymmetry via detergent reconstitution. Proteinase K digestion of 
      proteins had little effect on domain stability in NEM PMVs. We conclude that loss 
      of PMV lipid asymmetry can induce ordered domain formation. The dynamic control 
      of lipid asymmetry in cells may regulate domain formation in plasma membranes.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kakuda, Shinako
AU  - Kakuda S
AD  - Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, 
      NY, USA.
FAU - Suresh, Pavana
AU  - Suresh P
AD  - Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, 
      NY, USA.
FAU - Li, Guangtao
AU  - Li G
AD  - Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, 
      NY, USA.
FAU - London, Erwin
AU  - London E
AD  - Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, 
      NY, USA. Electronic address: erwin.london@stonybrook.edu.
LA  - eng
GR  - R35 GM122493/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211126
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Membrane Lipids)
SB  - IM
MH  - *Membrane Lipids
PMC - PMC8953672
OTO - NOTNLM
OT  - N-ethyl maleimide
OT  - annexin
OT  - dithiothreitol
OT  - fluorescence anisotropy
OT  - fluorescence resonance energy transfer
OT  - leaflet asymmetry
OT  - lipid rafts
OT  - liquid ordered
OT  - membrane domains
OT  - plasma membrane vesicles
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2021/11/30 06:00
MHDA- 2022/03/24 06:00
PMCR- 2021/11/26
CRDT- 2021/11/29 20:11
PHST- 2021/11/05 00:00 [received]
PHST- 2021/11/23 00:00 [revised]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2021/11/30 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2021/11/29 20:11 [entrez]
PHST- 2021/11/26 00:00 [pmc-release]
AID - S0022-2275(21)00138-3 [pii]
AID - 100155 [pii]
AID - 10.1016/j.jlr.2021.100155 [doi]
PST - ppublish
SO  - J Lipid Res. 2022 Jan;63(1):100155. doi: 10.1016/j.jlr.2021.100155. Epub 2021 Nov 
      26.