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Title: Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol

Journal Article · · Journal of Biological Chemistry
 [1];  [1];  [1];  [2];  [2];  [3];  [4]
  1. Univ. of Illinois, Urbana, IL (United States)
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. National Institutes of Health, Bethesda, MD (United States)
  4. Univ. of Illinois, Urbana, IL (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

The plasma membranes of mammalian cells are widely expected to contain domains that are enriched with cholesterol and sphingolipids. In this work, we have used high-resolution secondary ion mass spectrometry to directly map the distributions of isotope-labeled cholesterol and sphingolipids in the plasma membranes of intact fibroblast cells. Although acute cholesterol depletion reduced sphingolipid domain abundance, cholesterol was evenly distributed throughout the plasma membrane and was not enriched within the sphingolipid domains. As a result, we rule out favorable cholesterol-sphingolipid interactions as dictating plasma membrane organization in fibroblast cells. Because the sphingolipid domains are disrupted by drugs that depolymerize the cells actin cytoskeleton, cholesterol must instead affect the sphingolipid organization via an indirect mechanism that involves the cytoskeleton.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1313553
Report Number(s):
LLNL-JRNL-638518
Journal Information:
Journal of Biological Chemistry, Vol. 288, Issue 23; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 110 works
Citation information provided by
Web of Science

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The mystery of membrane organization: composition, regulation and roles of lipid rafts journal March 2017
Regulation of monoamine transporters and receptors by lipid microdomains: implications for depression journal June 2018
Mesoscale organization of domains in the plasma membrane – beyond the lipid raft journal February 2018
Lipid domain–dependent regulation of single-cell wound repair journal June 2014
NanoSIMS imaging: an approach for visualizing and quantifying lipids in cells and tissues journal October 2016
Endogenous sphingomyelin segregates into submicrometric domains in the living erythrocyte membrane journal May 2014
Cholesterol-pyrene as a probe for cholesterol distribution on ordered and disordered membranes: Determination of spectral wavelengths journal August 2018
Interleaflet Coupling, Pinning, and Leaflet Asymmetry—Major Players in Plasma Membrane Nanodomain Formation journal January 2017
Crystallization around solid-like nanosized docks can explain the specificity, diversity, and stability of membrane microdomains journal March 2014
Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter journal May 2018
Role of MCC/Eisosome in Fungal Lipid Homeostasis journal July 2019
Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis journal April 2017