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LAPTM4B controls the sphingolipid and ether lipid signature of small extracellular vesicles

Andrea Dichlberger1, Kecheng Zhou1, Nils Bäck2

  • 1Department of Anatomy and Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.

Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids
|November 12, 2020
PubMed

Insights

Lysosome Associated Protein Transmembrane 4B (LAPTM4B) influences small extracellular vesicle (sEV) lipid composition. LAPTM4B protein sorting determines sEV glycosphingolipid content and membrane stability.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Lipidomics

Background:

  • Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is a transmembrane protein involved in mTORC1 signaling.
  • Small extracellular vesicles (sEVs) are released by cells and found in biological fluids, playing roles in intercellular communication.

Purpose of the Study:

  • To investigate the role of LAPTM4B in the sorting and release of sEVs.
  • To determine how LAPTM4B affects the lipid composition and membrane properties of sEVs.

Main Methods:

  • LAPTM4B knockout and mutant expression in cells.
  • Analysis of LAPTM4B sorting into intraluminal vesicles (ILVs) and sEVs.
  • Unbiased lipidomic analysis of sEVs.
  • Assessment of sEV membrane nanodomain stability.

Main Results:

  • LAPTM4B is sorted into ILVs and released in sEVs, dependent on its third transmembrane domain (SLim).
  • LAPTM4B deficiency or SLim mutation leads to altered glycosphingolipid and ether lipid profiles in sEVs.
  • Changes in sEV lipid composition correlate with increased membrane nanodomain stability.

Conclusions:

  • LAPTM4B is a key determinant of sEV glycosphingolipid content and membrane properties.
  • The SLim motif of LAPTM4B is crucial for its function in modulating sEV lipid composition.
  • LAPTM4B influences the biophysical characteristics of sEVs through its impact on lipid profiles.
Keywords:
Ether lipidsExosomesExtracellular vesiclesGlycosphingolipidsMembrane nanodomainsSphingolipids

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