ORP5 and ORP8 bind phosphatidylinositol-4,5-biphosphate (PtdIns(4,5)P2) and regulate its level at the plasma membrane

被引：139

作者：

Ghai, Rajesh ^{[1
,4
]}

Du, Ximing ^{[1
]}

Wang, Huan ^{[2
]}

Dong, Jiangqing ^{[2
]}

Ferguson, Charles ^{[3
,4
]}

Brown, Andrew J. ^{[1
]}

Parton, Robert G. ^{[3
,4
]}

Wu, Jia-Wei ^{[2
]}

Yang, Hongyuan ^{[1
]}

机构：

[1] Univ New South Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia

[2] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, MOE Key Lab Prot Sci, Tsinghua Peking Ctr Life Sci,Sch Life Sci, Beijing 100084, Peoples R China

[3] Univ Queensland, Ctr Microscopy & Microanal, St Lucia, Qld 4072, Australia

[4] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 澳大利亚研究理事会;

关键词：

PLECKSTRIN HOMOLOGY DOMAINS; STEROL TRANSPORT; CONTACT SITES; PROTEINS; PHOSPHOINOSITIDES; PHOSPHATIDYLSERINE; DETERMINANTS; METABOLISM; EXCHANGE; NIR2;

D O I：

10.1038/s41467-017-00861-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

ORP5 and ORP8, members of the oxysterol-binding protein (OSBP)-related proteins (ORP) family, are endoplasmic reticulum membrane proteins implicated in lipid trafficking. ORP5 and ORP8 are reported to localize to endoplasmic reticulum-plasma membrane junctions via binding to phosphatidylinositol-4-phosphate (PtdIns(4)P), and act as a PtdIns(4)P/phosphatidylserine counter exchanger between the endoplasmic reticulum and plasma membrane. Here we provide evidence that the pleckstrin homology domain of ORP5/8 via PtdIns(4,5)P-2, and not PtdIns(4)P binding mediates the recruitment of ORP5/8 to endoplasmic reticulum-plasma membrane contact sites. The OSBP-related domain of ORP8 can extract and transport multiple phosphoinositides in vitro, and knocking down both ORP5 and ORP8 in cells increases the plasma membrane level of PtdIns(4,5)P-2 with little effect on PtdIns(4)P. Overall, our data show, for the first time, that phosphoinositides other than PtdIns (4)P can also serve as co-exchangers for the transport of cargo lipids by ORPs.

引用

页数：14

共 46 条

[31] A Four-Step Cycle Driven by PI(4)P Hydrolysis Directs Sterol/PI(4)P Exchange by the ER-Golgi Tether OSBP [J].