PMID- 33181324
OWN - NLM
STAT- MEDLINE
DCOM- 20210423
LR  - 20210423
IS  - 1879-2618 (Electronic)
IS  - 1388-1981 (Linking)
VI  - 1866
IP  - 2
DP  - 2021 Feb
TI  - LAPTM4B controls the sphingolipid and ether lipid signature of small 
      extracellular vesicles.
PG  - 158855
LID - S1388-1981(20)30247-X [pii]
LID - 10.1016/j.bbalip.2020.158855 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Dichlberger, Andrea
AU  - Dichlberger A
AD  - Department of Anatomy and Research Programs Unit, Faculty of Medicine, University 
      of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical 
      Research, Helsinki, Finland. Electronic address: andrea.dichlberger@helsinki.fi.
FAU - Zhou, Kecheng
AU  - Zhou K
AD  - Department of Anatomy and Research Programs Unit, Faculty of Medicine, University 
      of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical 
      Research, Helsinki, Finland. Electronic address: kecheng.zhou@helsinki.fi.
FAU - Back, Nils
AU  - Back N
AD  - Department of Anatomy and Research Programs Unit, Faculty of Medicine, University 
      of Helsinki, Helsinki, Finland. Electronic address: nils.back@helsinki.fi.
FAU - Nyholm, Thomas
AU  - Nyholm T
AD  - Biochemistry, Faculty of Science and Engineering, Abo Akademi University, Turku, 
      Finland. Electronic address: thomas.nyholm@abo.fi.
FAU - Backman, Anders
AU  - Backman A
AD  - Biochemistry, Faculty of Science and Engineering, Abo Akademi University, Turku, 
      Finland. Electronic address: andersba@abo.fi.
FAU - Mattjus, Peter
AU  - Mattjus P
AD  - Biochemistry, Faculty of Science and Engineering, Abo Akademi University, Turku, 
      Finland. Electronic address: Peter.Mattjus@abo.fi.
FAU - Ikonen, Elina
AU  - Ikonen E
AD  - Department of Anatomy and Research Programs Unit, Faculty of Medicine, University 
      of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical 
      Research, Helsinki, Finland. Electronic address: elina.ikonen@helsinki.fi.
FAU - Blom, Tomas
AU  - Blom T
AD  - Department of Anatomy and Research Programs Unit, Faculty of Medicine, University 
      of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical 
      Research, Helsinki, Finland. Electronic address: tomas.blom@helsinki.fi.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201110
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Biol Lipids
JT  - Biochimica et biophysica acta. Molecular and cell biology of lipids
JID - 101731727
RN  - 0 (Glycosphingolipids)
RN  - 0 (LAPTM4B protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oncogene Proteins)
SB  - IM
MH  - Cell Line, Tumor
MH  - Endosomes/metabolism
MH  - Exosomes/*metabolism
MH  - Gene Knockout Techniques
MH  - Glycosphingolipids/*metabolism
MH  - Humans
MH  - Lipid Metabolism
MH  - Lipidomics
MH  - Membrane Proteins/genetics/*metabolism
MH  - Oncogene Proteins/genetics/*metabolism
OTO - NOTNLM
OT  - Ether lipids
OT  - Exosomes
OT  - Extracellular vesicles
OT  - Glycosphingolipids
OT  - Membrane nanodomains
OT  - Sphingolipids
EDAT- 2020/11/13 06:00
MHDA- 2021/04/24 06:00
CRDT- 2020/11/12 20:10
PHST- 2020/06/18 00:00 [received]
PHST- 2020/11/03 00:00 [revised]
PHST- 2020/11/05 00:00 [accepted]
PHST- 2020/11/13 06:00 [pubmed]
PHST- 2021/04/24 06:00 [medline]
PHST- 2020/11/12 20:10 [entrez]
AID - S1388-1981(20)30247-X [pii]
AID - 10.1016/j.bbalip.2020.158855 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Feb;1866(2):158855. doi: 
      10.1016/j.bbalip.2020.158855. Epub 2020 Nov 10.