Molecular determinants of ER-Golgi contacts identified through a new FRET-FLIM system.
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:
04 03 2019
04 03 2019
Historique:
received:
05
12
2018
revised:
14
12
2018
accepted:
18
12
2018
pubmed:
20
1
2019
medline:
27
2
2020
entrez:
20
1
2019
Statut:
ppublish
Résumé
ER-TGN contact sites (ERTGoCS) have been visualized by electron microscopy, but their location in the crowded perinuclear area has hampered their analysis via optical microscopy as well as their mechanistic study. To overcome these limits we developed a FRET-based approach and screened several candidates to search for molecular determinants of the ERTGoCS. These included the ER membrane proteins VAPA and VAPB and lipid transfer proteins possessing dual (ER and TGN) targeting motifs that have been hypothesized to contribute to the maintenance of ERTGoCS, such as the ceramide transfer protein CERT and several members of the oxysterol binding proteins. We found that VAP proteins, OSBP1, ORP9, and ORP10 are required, with OSBP1 playing a redundant role with ORP9, which does not involve its lipid transfer activity, and ORP10 being required due to its ability to transfer phosphatidylserine to the TGN. Our results indicate that both structural tethers and a proper lipid composition are needed for ERTGoCS integrity.
Identifiants
pubmed: 30659100
pii: jcb.201812020
doi: 10.1083/jcb.201812020
pmc: PMC6400564
doi:
Substances chimiques
Membrane Lipids
0
Receptors, Steroid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1055-1065Subventions
Organisme : European Research Council
ID : 670881
Pays : International
Organisme : Telethon
ID : TGM11CB1
Pays : Italy
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 Venditti et al.
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