Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 regulates endocytic recycling.
Spatiotemporal control of phosphatidylinositol 4-phosphate by Sac2 regulates endocytic recycling.
复制标题
SAC2通过SAC2调节内吞回收的磷脂酰肌醇4-磷酸的时空控制。
DOI：
10.1083/jcb.201408027
复制
发表时间：
2015-04-13
期刊：
影响因子：
--
通讯作者：
Mao Y
中科院分区：
文献类型：
--
作者：
Hsu F;Hu F;Mao Y
Sac 2（INPP 5 F）是一种磷酸肌醇4-磷酸酶，其特异性水解PI（4）P并调节内吞再循环。磷酸肌醇（PI）代谢酶级联反应产生和周转的空间和时间限制是内吞途径中的关键调节机制。在这里，我们证明，Sac 1域含有蛋白Sac 2是PI 4-磷酸酶，特异性水解磷脂酰肌醇4-磷酸在体外。我们进一步表明，Sac 2与早期内体标记共定位，并被招募到转铁蛋白（Tfn）的囊泡内吞回收过程中。外源表达的催化失活突变体Sac 2C 458 S导致Tfn受体的细胞分布改变和延迟Tfn再循环。此外，Sac 2的基因组切除对Tfn和整联蛋白再循环以及细胞迁移的缺陷引起类似的扰动。Sac 2的结构表征揭示了一个独特的pleckstrin样同源Sac 2结构域保守的所有Sac 2直向同源物。总的来说，我们的研究结果为Sac 2在内吞再循环途径中对PI的严格调控提供了证据。
Sac2 (INPP5F) is a phosphoinositide 4-phosphatase that specifically hydrolyzes PI(4)P and regulates endocytic recycling. It is well established that the spatial- and temporal-restricted generation and turnover of phosphoinositides (PIs) by a cascade of PI-metabolizing enzymes is a key regulatory mechanism in the endocytic pathway. Here, we demonstrate that the Sac1 domain–containing protein Sac2 is a PI 4-phosphatase that specifically hydrolyzes phosphatidylinositol 4-phosphate in vitro. We further show that Sac2 colocalizes with early endosomal markers and is recruited to transferrin (Tfn)-containing vesicles during endocytic recycling. Exogenous expression of the catalytically inactive mutant Sac2C458S resulted in altered cellular distribution of Tfn receptors and delayed Tfn recycling. Furthermore, genomic ablation of Sac2 caused a similar perturbation on Tfn and integrin recycling as well as defects in cell migration. Structural characterization of Sac2 revealed a unique pleckstrin-like homology Sac2 domain conserved in all Sac2 orthologues. Collectively, our findings provide evidence for the tight regulation of PIs by Sac2 in the endocytic recycling pathway.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1016/s0006-291x(02)00320-0
发表时间：
2002-05-10
影响因子：
3.1
作者：
Kuroda, TS;Fukuda, M;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
3.5
作者：
Kremer, Thomas;Kempf, Christian;Dresbach, Thomas
通讯作者：
Dresbach, Thomas
影响因子：
9.8
作者：
Chow, Clement Y.;Landers, John E.;Meisler, Miriam H.
通讯作者：
Meisler, Miriam H.
影响因子：
3.7
作者：
Adler, Jeremy;Parmryd, Ingela
通讯作者：
Parmryd, Ingela