Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission.
Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission.
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DOI：
10.1016/j.devcel.2010.12.008
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发表时间：
2011-02-15
影响因子：
11.8
通讯作者：
Di Paolo, Gilbert
中科院分区：
文献类型：
--
作者：
Chang-Ileto, Belle;Frere, Samuel G.;Chan, Robin B.;Voronov, Sergey V.;Roux, Aurelian;Di Paolo, Gilbert
磷脂酰肌醇-4，5-二磷酸[PI（4，5）P2]在网格蛋白介导的内吞作用中起重要作用。然而，PI（4，5）P2代谢在膜内化过程中如何在空间和时间上进行调节以及内吞偶联PI（4，5）P2去磷酸化的功能后果仍有待探索。使用不同曲率的脂质体的无细胞测定，我们表明，主要的突触磷酸肌醇磷酸酶，synaptojanin 1（Synj 1），与膜曲率发生器/传感器，如BAR蛋白质内亲和素，优先删除PI（4，5）P2从弯曲的膜，而不是相对平坦的。此外，在体内招聘Synj 1的肌醇5-磷酸酶结构域的endophilin诱导的膜小管的结果，这些结构的碎片和缩合，主要是在动力依赖的方式。我们的研究提出了一种可能性，即基于几何结构的机制可能有助于在膜内化过程中空间限制PI（4，5）P2消除，并表明Synj 1在高曲率位点实现的PI（4，5）P2-至-PI 4P转换可能与发动蛋白合作实现膜分裂。
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] plays a fundamental role in clathrin-mediated endocytosis. However, precisely how PI(4,5)P2 metabolism is spatially and temporally regulated during membrane internalization and the functional consequences of endocytosis-coupled PI(4,5)P2 dephosphorylation remain to be explored. Using cell free assays with liposomes of varying curvatures, we show that the major synaptic phosphoinositide phosphatase, synaptojanin 1 (Synj1), acts with membrane curvature generators/sensors, such as the BAR protein endophilin, to preferentially remove PI(4,5)P2 from curved membranes as opposed to relatively flat ones. Moreover, in vivo recruitment of Synj1’s inositol 5-phosphatase domain to endophilin-induced membrane tubules results in fragmentation and condensation of these structures largely in a dynamin-dependent fashion. Our study raises the possibility that geometry-based mechanisms may contribute to spatially restricting PI(4,5)P2 elimination during membrane internalization and suggests that the PI(4,5)P2-to-PI4P conversion achieved by Synj1 at sites of high curvature may cooperate with dynamin to achieve membrane fission.
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DOI：
10.1083/jcb.150.3.589
发表时间：
2000-08-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harris TW;Hartwieg E;Horvitz HR;Jorgensen EM
通讯作者：
Jorgensen EM
影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
25
作者：
Berman, Diego E.;Dall'Armi, Claudia;Di Paolo, Gilbert
通讯作者：
Di Paolo, Gilbert
影响因子：
64.8
作者：
Ford, MGJ;Mills, IG;McMahon, HT
通讯作者：
McMahon, HT
影响因子：
11.4
作者：
Gallop, Jennifer L.;Jao, Christine C.;T McMahon, Harvey
通讯作者：
T McMahon, Harvey