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ORP5和ORP8结合磷脂酰肌醇-4,5-二磷酸（PtdIns(4,5)P₂）并调节其在质膜上的水平。

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

作者信息

Ghai Rajesh, Du Ximing, Wang Huan, Dong Jiangqing, Ferguson Charles, Brown Andrew J, Parton Robert G, Wu Jia-Wei, Yang Hongyuan

机构信息

School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia.

出版信息

Nat Commun. 2017 Oct 2;8(1):757. doi: 10.1038/s41467-017-00861-5.

DOI:10.1038/s41467-017-00861-5
PMID:28970484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5624964/
Abstract

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 , 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 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.ORP5/8 are endoplasmic reticulum (ER) membrane proteins implicated in lipid trafficking that localize to ER-plasma membrane (PM) contacts and maintain membrane homeostasis. Here the authors show that PtdIns(4,5)P plays a critical role in the targeting and function of ORP5/8 at the PM.

摘要

氧化甾醇结合蛋白（OSBP）相关蛋白（ORP）家族成员ORP5和ORP8是参与脂质转运的内质网膜蛋白。据报道，ORP5和ORP8通过与磷脂酰肌醇-4-磷酸（PtdIns(4)P）结合而定位于内质网-质膜交界处，并在内质网和质膜之间充当PtdIns(4)P/磷脂酰丝氨酸反向交换器。在此，我们提供证据表明，ORP5/8的普列克底物蛋白同源结构域通过与磷脂酰肌醇-4,5-二磷酸（PtdIns(4,5)P）而非PtdIns(4)P结合，介导ORP5/8募集到内质网-质膜接触位点。ORP8的OSBP相关结构域在体外能够提取和转运多种磷酸肌醇，在细胞中敲低ORP5和ORP8均会增加质膜上PtdIns(4,5)P的水平，而对PtdIns(4)P影响不大。总体而言，我们的数据首次表明，除PtdIns(4)P之外的磷酸肌醇也可作为ORP转运脂质货物的共交换剂。ORP5/8是参与脂质转运的内质网（ER）膜蛋白，定位于内质网-质膜（PM）接触位点并维持膜稳态。本文作者表明，PtdIns(4,5)P在ORP5/8定位于质膜及其功能发挥中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/cd305b81e516/41467_2017_861_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/8cfcbed2b477/41467_2017_861_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/da50b5e1ca20/41467_2017_861_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/d549856186b8/41467_2017_861_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/1cb95316f2ba/41467_2017_861_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/24ccddbc97e4/41467_2017_861_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/cd305b81e516/41467_2017_861_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/8cfcbed2b477/41467_2017_861_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/da50b5e1ca20/41467_2017_861_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/d549856186b8/41467_2017_861_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/1cb95316f2ba/41467_2017_861_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/24ccddbc97e4/41467_2017_861_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a497/5624964/cd305b81e516/41467_2017_861_Fig6_HTML.jpg

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2
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3
The role of phosphatidylinositol-transfer proteins at membrane contact sites.
Mol Med. 2025 May 30;31(1):213. doi: 10.1186/s10020-025-01275-6.
4
ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.ATP8B1调节磷脂酰肌醇-4,5-二磷酸（PIP2）的定位以及焦亡执行者Gasdermin D的切割。
Proc Natl Acad Sci U S A. 2025 Jun 3;122(22):e2502798122. doi: 10.1073/pnas.2502798122. Epub 2025 May 29.
5
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Membranes (Basel). 2025 May 16;15(5):154. doi: 10.3390/membranes15050154.
6
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J Cell Biol. 2025 Jul 7;224(7). doi: 10.1083/jcb.202403126. Epub 2025 May 2.
7
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Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jun;1870(5):159615. doi: 10.1016/j.bbalip.2025.159615. Epub 2025 Apr 20.
8
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10
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