Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway.

Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic pathway.
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SAC2/INPP5F是一种在内吞途径中起作用的肌醇4-磷酸酶。

DOI:
10.1083/jcb.201409064
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发表时间:
2015-04-13
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
De Camilli P
De Camilli P
中科院分区:
其他
文献类型:
--
作者:
Nakatsu F;Messa M;Nández R;Czapla H;Zou Y;Strittmatter SM;De Camilli P

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Sac 2/INPP 5 F在内吞途径中的功能及其作为4-磷酸酶的活性表明Sac 2/INPP 5 F和OCRL可能在PI(4,5)P2的顺序去磷酸化中以模仿synaptojanin的两个磷酸酶模块的伙伴关系合作。肌醇磷酸酶向胞吞膜的募集介导PI(4,5)P2(一种浓缩在质膜中的磷酸肌醇)的去磷酸化,并防止其在核内体上积累。内吞作用期间PI(4,5)P2转化为PtdIns的重要性通过突触Janins中5-磷酸酶和4-磷酸酶(Sac结构域)模块、从酵母到人保守的内吞PI(4,5)P2磷酸酶和酵母中唯一的PI(4,5)P2磷酸酶的存在而证明。OCRL是另一种将内吞作用与PI(4,5)P2去磷酸化偶联的5-磷酸酶,缺乏Sac结构域。在这里,我们表明,Sac 2/INPP 5 F是一个PI 4P磷酸酶,共定位与OCRL的内吞膜,包括由网格蛋白介导的内吞作用,macropinosomes,和Rab 5内体形成的囊泡。OCRL-Sac 2/INPP 5 F相互作用可以通过免疫共沉淀来证明,并且通过Rab 5来增强,Rab 5的活性是将Sac 2/INPP 5 F募集到内体所必需的。Sac 2/INPP 5 F和OCRL可能在肌醇的5和4位的PI(4,5)P2的顺序去磷酸化中合作,这种合作关系模仿synaptojanin的两个磷酸酶模块。
The function of Sac2/INPP5F in the endocytic pathway and its activity as a 4-phosphatase suggest that Sac2/INPP5F and OCRL may cooperate in the sequential dephosphorylation of PI(4,5)P2 in a partnership that mimics that of the two phosphatase modules of synaptojanin. The recruitment of inositol phosphatases to endocytic membranes mediates dephosphorylation of PI(4,5)P2, a phosphoinositide concentrated in the plasma membrane, and prevents its accumulation on endosomes. The importance of the conversion of PI(4,5)P2 to PtdIns during endocytosis is demonstrated by the presence of both a 5-phosphatase and a 4-phosphatase (Sac domain) module in the synaptojanins, endocytic PI(4,5)P2 phosphatases conserved from yeast to humans and the only PI(4,5)P2 phosphatases in yeast. OCRL, another 5-phosphatase that couples endocytosis to PI(4,5)P2 dephosphorylation, lacks a Sac domain. Here we show that Sac2/INPP5F is a PI4P phosphatase that colocalizes with OCRL on endocytic membranes, including vesicles formed by clathrin-mediated endocytosis, macropinosomes, and Rab5 endosomes. An OCRL–Sac2/INPP5F interaction could be demonstrated by coimmunoprecipitation and was potentiated by Rab5, whose activity is required to recruit Sac2/INPP5F to endosomes. Sac2/INPP5F and OCRL may cooperate in the sequential dephosphorylation of PI(4,5)P2 at the 5 and 4 position of inositol in a partnership that mimics that of the two phosphatase modules of synaptojanin.
Rab5和Appl1将OCRL和INPP5B募集到吞噬体中,消耗了磷酸肌醇,并减轻AKT信号传导。
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