PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.
PI4P/PS countertransport by ORP10 at ER-endosome membrane contact sites regulates endosome fission.
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DOI：
10.1083/jcb.202103141
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发表时间：
2022-01-03
期刊：
影响因子：
--
通讯作者：
Nakatsu F
中科院分区：
文献类型：
--
作者：
Kawasaki A;Sakai A;Nakanishi H;Hasegawa J;Taguchi T;Sasaki J;Arai H;Sasaki T;Igarashi M;Nakatsu F
ORP 10以PI 4P依赖的方式定位于由ORP 9和VAP束缚的ER-内体膜接触位点，在那里它介导PI 4P和PS的反向转运。这反过来又为内体提供PS，从而促进EHD 1募集和内体分裂。膜接触位点（MCSs）是氧化固醇结合蛋白（OSBP）相关蛋白（ORP）进行非囊泡脂质转运的区域。ORPs介导脂质反向转运，其中两种不同的脂质反向转运。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。我们报告说，在ER-内体MCSs的ORP 10的脂质逆向转运调节逆行膜贩运。ORP 10与ORP 9和VAP一起以磷脂酰肌醇4-磷酸（PI 4P）依赖性方式形成ER-内体MCS。ORP 10在体外脂质体之间以及ER与内体之间表现出对其配体PI 4 P和磷脂酰丝氨酸（PS）的脂质交换活性。细胞生物学分析表明，ORP 10提供了一个池的PS从ER，在交换PI 4P，到内涵体的PS结合蛋白EHD 1被招募，以促进内涵体分裂。我们的研究强调了ER-内体MCSs的一种新的脂质交换，作为一种非酶促PI 4P-PS转化机制，在逆行膜运输过程中组织膜重塑。
ORP10 localizes in a PI4P-dependent manner at ER–endosome membrane contact sites tethered by ORP9 and VAP, where it mediates countertransport of PI4P and PS. This in turn supplies endosomes with PS, thereby promoting EHD1 recruitment and endosome fission. 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.
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DOI：
10.1083/jcb.201609033
发表时间：
2017-05-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Allison R;Edgar JR;Pearson G;Rizo T;Newton T;Günther S;Berner F;Hague J;Connell JW;Winkler J;Lippincott-Schwartz J;Beetz C;Winner B;Reid E
通讯作者：
Reid E
影响因子：
16.6
作者：
Ghai R;Du X;Wang H;Dong J;Ferguson C;Brown AJ;Parton RG;Wu JW;Yang H
通讯作者：
Yang H
影响因子：
7.2
作者：
Gautreau, Alexis;Oguievetskaia, Ksenia;Ungermann, Christian
通讯作者：
Ungermann, Christian
DOI：
10.1126/science.aab1370
发表时间：
2015-07-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chung J;Torta F;Masai K;Lucast L;Czapla H;Tanner LB;Narayanaswamy P;Wenk MR;Nakatsu F;De Camilli P
通讯作者：
De Camilli P
影响因子：
3.5
作者：
Blondeau, F;Laporte, J;Mandel, JL
通讯作者：
Mandel, JL