Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling
Stonin 2 is an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling
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DOI：
10.1016/j.devcel.2005.12.011
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发表时间：
2006-02-01
影响因子：
11.8
通讯作者：
Haucke, V
中科院分区：
文献类型：
--
作者：
Diril, MK;Wienisch, M;Haucke, V
笼蛋白介导的内吞作用参与了循环膜受体的内化、循环和降解，也参与了突触囊泡蛋白的生物发生。虽然许多组成性内化的货物蛋白是由笼蛋白适配器复合体AP-2直接识别的，但依赖刺激的膜蛋白内吞作用通常是由专门的分选适配器促进的。虽然笼蛋白介导的内吞作用似乎是突触前囊泡循环的主要途径，但在哺乳动物中还没有发现专用于突触囊泡膜蛋白内吞的分选适配子。在这里，我们证明了ston2，一个被石头砸到B的果蝇的哺乳动物同源基因，促进了依赖于clathrin/AP-2的突触素的内化，并将其靶向于活神经元中一个循环的囊泡池。斯通宁2促进突触素内吞的能力依赖于它与AP-2的结合，AP-2是一个完整的单位同源结构域，以及功能上的AP-2异构体。我们的数据证明stin2是一种依赖AP-2的内吞分选适配器，用于突触凝集素的内化和再循环。
Clathrin-mediated endocytosis is involved in the internalization, recycling, and degradation of cycling membrane receptors as well as in the biogenesis of synaptic vesicle proteins. While many constitutively internalized cargo proteins are recognized directly by the clathrin adaptor complex AP-2, stimulation-dependent endocytosis of membrane proteins is often facilitated by specialized sorting adaptors. Although clathrin-mediated endocytosis appears to be a major pathway for presynaptic vesicle cycling, no sorting adaptor dedicated to synaptic vesicle membrane protein endocytosis has been indentified in mammals. Here, we show that stonin 2, a mammalian ortholog of Drosophila stoned B, facilitates clathrin/AP-2-dependent internalization of synaptotagmin and targets it to a recycling vesicle pool in living neurons. The ability of stonin 2 to facilitate endocytosis of synaptotagmin is dependent on its association with AP-2, an intact mu-homology domain, and functional AP-2 heterotetramers. Our data identify stonin 2 as an AP-2-dependent endocytic sorting adaptor for synaptotagmin internalization and recycling.