Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles.
AlphaFold2
CERT
ER-endosome contact sites
HPA-12
NC03
PI4KIIIβ
PI4KIIIβ-IN-10
PI4KIIα
PI4P
Tsg101
ceramide
extracellular vesicles
sphingomyelin
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
10
05
2022
received:
27
08
2021
accepted:
11
05
2022
entrez:
1
6
2022
pubmed:
2
6
2022
medline:
3
6
2022
Statut:
ppublish
Résumé
The formation of extracellular vesicles (EVs) is induced by the sphingolipid ceramide. How this pathway is regulated is not entirely understood. Here, we report that the ceramide transport protein (CERT) mediates a non-vesicular transport of ceramide between the endoplasmic reticulum (ER) and the multivesicular endosome at contact sites. The process depends on the interaction of CERT's PH domain with PI4P generated by PI4KIIα at endosomes. Furthermore, a complex is formed between the START domain of CERT, which carries ceramide, and the Tsg101 protein, which is part of the endosomal sorting complex required for transport (ESCRT-I). Inhibition of ceramide biosynthesis reduces CERT-Tsg101 complex formation. Overexpression of CERT increases EV secretion while its inhibition reduces EV formation and the concentration of ceramides and sphingomyelins in EVs. In conclusion, we discovered a function of CERT in regulating the sphingolipid composition and biogenesis of EVs, which links ceramide to the ESCRT-dependent pathway.
Identifiants
pubmed: 35642450
doi: 10.1002/jev2.12233
pmc: PMC9156972
doi:
Substances chimiques
Carrier Proteins
0
Ceramides
0
Endosomal Sorting Complexes Required for Transport
0
Sphingolipids
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12233Subventions
Organisme : NINDS NIH HHS
ID : R01 NS095215
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028383
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103436
Pays : United States
Organisme : BLRD VA
ID : I01 BX003643
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016059
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG034389
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072946
Pays : United States
Organisme : ZonMw
ID : 733050105
Pays : Netherlands
Organisme : NIA NIH HHS
ID : R01 AG064234
Pays : United States
Informations de copyright
© 2022 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
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