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内质网-内体膜接触位点上的 ORP10 介导的 PI4P/PS 反向转运调节内体裂变。

PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.

机构信息

Department of Neurochemistry and Molecular Cell Biology, Niigata University School of Medicine and Graduate School of Medical/Dental Sciences, Niigata, Japan.

Graduate School of Medicine and Research Center for Biosignal, Akita University, Akita, Japan.

出版信息

J Cell Biol. 2022 Jan 3;221(1). doi: 10.1083/jcb.202103141. Epub 2021 Nov 24.

DOI:10.1083/jcb.202103141
PMID:34817532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8624802/
Abstract

Membrane contact sites (MCSs) serve as a zone for nonvesicular lipid transport by oxysterol-binding protein (OSBP)-related proteins (ORPs). ORPs mediate lipid countertransport, in which two distinct lipids are transported counterdirectionally. How such lipid countertransport controls specific biological functions, however, remains elusive. We report that lipid countertransport by ORP10 at ER-endosome MCSs regulates retrograde membrane trafficking. ORP10, together with ORP9 and VAP, formed ER-endosome MCSs in a phosphatidylinositol 4-phosphate (PI4P)-dependent manner. ORP10 exhibited a lipid exchange activity toward its ligands, PI4P and phosphatidylserine (PS), between liposomes in vitro, and between the ER and endosomes in situ. Cell biological analysis demonstrated that ORP10 supplies a pool of PS from the ER, in exchange for PI4P, to endosomes where the PS-binding protein EHD1 is recruited to facilitate endosome fission. Our study highlights a novel lipid exchange at ER-endosome MCSs as a nonenzymatic PI4P-to-PS conversion mechanism that organizes membrane remodeling during retrograde membrane trafficking.

摘要

膜接触位点 (MCSs) 充当了固醇结合蛋白 (OSBP) 相关蛋白 (ORPs) 非囊泡脂质运输的区域。ORPs 介导脂质反向转运，其中两种不同的脂质被反向运输。然而，这种脂质反向转运如何控制特定的生物学功能仍然难以捉摸。我们报告称，ORP10 在 ER-内体 MCSs 处的脂质反向转运调节逆行膜运输。ORP10 与 ORP9 和 VAP 一起以磷脂酰肌醇 4-磷酸 (PI4P) 依赖性方式形成 ER-内体 MCSs。ORP10 在体外脂质体之间以及原位 ER 和内体之间表现出对其配体 PI4P 和磷脂酰丝氨酸 (PS) 的脂质交换活性。细胞生物学分析表明，ORP10 从 ER 供应 PS 池，以换取 PI4P，从而将 PS 结合蛋白 EHD1 募集到内体以促进内体分裂。我们的研究强调了 ER-内体 MCSs 处的新型脂质交换作为一种非酶 PI4P 到 PS 转化机制，该机制在逆行膜运输过程中组织了膜重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/3cd793575fc0/JCB_202103141_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/d2b1e4732536/JCB_202103141_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/b2951a113996/JCB_202103141_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/9a4dbc0e0d04/JCB_202103141_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/121c9ae6cf75/JCB_202103141_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/184f6adca76c/JCB_202103141_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/46a90e3c4a6d/JCB_202103141_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/3cd793575fc0/JCB_202103141_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/d2b1e4732536/JCB_202103141_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/b2951a113996/JCB_202103141_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/9a4dbc0e0d04/JCB_202103141_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/121c9ae6cf75/JCB_202103141_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/184f6adca76c/JCB_202103141_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/46a90e3c4a6d/JCB_202103141_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ea6/8624802/3cd793575fc0/JCB_202103141_FigS3.jpg

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