PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER - Plasma membrane contacts

Jeeyun Chung; Federico Torta; Kaori Masai; Louise Lucast; Heather Czapla; Lukas B. Tanner; Pradeep Narayanaswamy; Markus R. Wenk; Fubito Nakatsu; Pietro De Camilli

doi:10.1126/science.aab1370

PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER - Plasma membrane contacts

Jeeyun Chung, Federico Torta, Kaori Masai, Louise Lucast, Heather Czapla, Lukas B. Tanner, Pradeep Narayanaswamy, Markus R. Wenk, Fubito Nakatsu, Pietro De Camilli^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

454 Citations (Scopus)

Abstract

Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP - related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

Original language	English
Pages (from-to)	428-432
Number of pages	5
Journal	Science
Volume	349
Issue number	6246
DOIs	https://doi.org/10.1126/science.aab1370
Publication status	Published - 24 Jul 2015
Externally published	Yes

Access to Document

10.1126/science.aab1370

Cite this

@article{bf4a4147d761479a9ba75015a66e7433,

title = "PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER - Plasma membrane contacts",

abstract = "Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP - related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.",

author = "Jeeyun Chung and Federico Torta and Kaori Masai and Louise Lucast and Heather Czapla and Tanner, {Lukas B.} and Pradeep Narayanaswamy and Wenk, {Markus R.} and Fubito Nakatsu and {De Camilli}, Pietro",

year = "2015",

month = jul,

day = "24",

doi = "10.1126/science.aab1370",

language = "English",

volume = "349",

pages = "428--432",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6246",

}

TY - JOUR

T1 - PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER - Plasma membrane contacts

AU - Chung, Jeeyun

AU - Torta, Federico

AU - Masai, Kaori

AU - Lucast, Louise

AU - Czapla, Heather

AU - Tanner, Lukas B.

AU - Narayanaswamy, Pradeep

AU - Wenk, Markus R.

AU - Nakatsu, Fubito

AU - De Camilli, Pietro

PY - 2015/7/24

Y1 - 2015/7/24

N2 - Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP - related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

AB - Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP - related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

UR - http://www.scopus.com/inward/record.url?scp=84938118007&partnerID=8YFLogxK

U2 - 10.1126/science.aab1370

DO - 10.1126/science.aab1370

M3 - Article

C2 - 26206935

AN - SCOPUS:84938118007

SN - 0036-8075

VL - 349

SP - 428

EP - 432

JO - Science

JF - Science

IS - 6246

ER -

PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER - Plasma membrane contacts

Abstract

Access to Document

Other files and links

Fingerprint

Cite this