Structure, functions and regulation of CERT, a lipid-transfer protein for the delivery of ceramide at the ER-Golgi membrane contact sites.
CERT1
FFAT motif
OSBP
PKD
functional regulation
intellectual disability
lipid-transfer protein
membrane contact sites
phosphorylation
sphingomyelin synthase
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
17
05
2019
revised:
26
06
2019
accepted:
26
06
2019
pubmed:
30
6
2019
medline:
19
6
2020
entrez:
30
6
2019
Statut:
ppublish
Résumé
The inter-organelle transport of lipids must be regulated to ensure appropriate lipid composition of each organelle. In mammalian cells, ceramide synthesised in the endoplasmic reticulum (ER) is transported to the trans-Golgi regions, where ceramide is converted to sphingomyelin (SM) with the concomitant production of diacylglycerol. Ceramide transport protein (CERT) transports ceramide from the ER to the trans-Golgi regions at the ER-Golgi membrane contact sites (MCS). The function of CERT is down-regulated by multisite phosphorylation of a serine-repeat motif (SRM) and up-regulated by phosphorylation of serine 315 in CERT. Multisite phosphorylation of the SRM is primed by protein kinase D, which is activated by diacylglycerol. The function of CERT is regulated by a phosphorylation-dependent feedback mechanism in response to cellular requirements of SM. CERT-dependent ceramide transport is also affected by the pool of phosphatidylinositol (PtdIns)-4-phosphate (PtdIns(4)P) in the trans-Golgi regions, while the PtdIns(4)P pool is regulated by PtdIns-4-kinases and oxysterol-binding protein. The ER-Golgi MCS may serve as inter-organelle communication zones, in which many factors work in concert to serve as an extensive rheostat of SM, diacylglycerol, cholesterol and PtdIns(4)P.
Identifiants
pubmed: 31254361
doi: 10.1002/1873-3468.13511
doi:
Substances chimiques
Ceramides
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2366-2377Subventions
Organisme : Japan Agency for Medical Research and Development
ID : JP18gm0910005j0004
Pays : International
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 17H06417
Pays : International
Organisme : JSPS
ID : 18K06649
Pays : International
Informations de copyright
© 2019 Federation of European Biochemical Societies.
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