ORP5 localizes to ER-lipid droplet contacts and regulates the level of PI(4)P on lipid droplets.
Endoplasmic Reticulum
/ metabolism
HEK293 Cells
Humans
Lipid Droplets
/ metabolism
Lipid Metabolism
Minor Histocompatibility Antigens
/ metabolism
Phosphatidylinositol Phosphates
/ metabolism
Phospholipid Transfer Proteins
/ metabolism
Phosphotransferases (Alcohol Group Acceptor)
/ metabolism
Receptors, Steroid
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
06 01 2020
06 01 2020
Historique:
received:
22
05
2019
revised:
17
09
2019
accepted:
03
10
2019
pubmed:
28
10
2019
medline:
28
7
2020
entrez:
27
10
2019
Statut:
ppublish
Résumé
Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in cellular metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. During LD biogenesis and growth, this monolayer of lipids expands by acquiring phospholipids from the endoplasmic reticulum (ER) through nonvesicular mechanisms. Here, in a mini-screen, we find that ORP5, an integral membrane protein of the ER, can localize to ER-LD contact sites upon oleate loading. ORP5 interacts with LDs through its ligand-binding domain, and ORP5 deficiency enhances neutral lipid synthesis and increases the size of LDs. Importantly, there is significantly more phosphatidylinositol-4-phosphate (PI(4)P) and less phosphatidylserine (PS) on LDs in ORP5-deficient cells than in normal cells. The increased presence of PI(4)P on LDs in ORP5-deficient cells requires phosphatidylinositol 4-kinase 2-α. Our results thus demonstrate the existence of PI(4)P on LDs and suggest that LD-associated PI(4)P may be primarily used by ORP5 to deliver PS to LDs.
Identifiants
pubmed: 31653673
pii: jcb.201905162
doi: 10.1083/jcb.201905162
pmc: PMC7039201
pii:
doi:
Substances chimiques
Minor Histocompatibility Antigens
0
Phosphatidylinositol Phosphates
0
Phospholipid Transfer Proteins
0
Receptors, Steroid
0
oxysterol binding protein
0
phosphatidylinositol 4-phosphate
0
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
phosphatidylinositol phosphate 4-kinase
EC 2.7.1.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 Du et al.
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