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

Andrea Dichlberger, Kecheng Zhou, Nils Bäck, Thomas Nyholm, Anders Backman, Peter Mattjus, Elina Ikonen, Tomas Blom

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Lysosome Associated Protein Transmembrane 4B (LAPTM4B) is a four-membrane spanning ceramide interacting protein that regulates mTORC1 signaling. Here, we show that LAPTM4B is sorted into intraluminal vesicles (ILVs) of multivesicular endosomes (MVEs) and released in small extracellular vesicles (sEVs) into conditioned cell culture medium and human urine. Efficient sorting of LAPTM4B into ILV membranes depends on its third transmembrane domain containing a sphingolipid interaction motif (SLim). Unbiased lipidomic analysis reveals a strong enrichment of glycosphingolipids in sEVs secreted from LAPTM4B knockout cells and from cells expressing a SLim-deficient LAPTM4B mutant. The altered sphingolipid profile is accompanied by a distinct SLim-dependent co-modulation of ether lipid species. The changes in the lipid composition of sEVs derived from LAPTM4B knockout cells is reflected by an increased stability of membrane nanodomains of sEVs. These results identify LAPTM4B as a determinant of the glycosphingolipid profile and membrane properties of sEVs.
OriginalspråkEngelska
Artikelnummer158855
TidskriftBiochimica et Biophysica Acta Molecular and Cell Biology of Lipids
Volym1866
Utgåva2
DOI
StatusPublicerad - 10 nov 2020
MoE-publikationstypA1 Tidskriftsartikel-refererad

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