Diril M Kasim, Wienisch Martin, Jung Nadja, Klingauf Jürgen, Haucke Volker
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Department of Membrane Biochemistry, Takustrasse 6, D-14195 Berlin, Germany.
Dev Cell. 2006 Feb;10(2):233-44. doi: 10.1016/j.devcel.2005.12.011.
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.
网格蛋白介导的内吞作用参与循环膜受体的内化、再循环和降解，以及突触小泡蛋白的生物合成。虽然许多组成型内化的货物蛋白直接被网格蛋白衔接复合物AP-2识别，但膜蛋白的刺激依赖性内吞作用通常由专门的分选衔接蛋白促进。尽管网格蛋白介导的内吞作用似乎是突触前小泡循环的主要途径，但在哺乳动物中尚未鉴定出专门用于突触小泡膜蛋白内吞作用的分选衔接蛋白。在这里，我们表明，哺乳动物中与果蝇stoned B同源的stonin 2促进网格蛋白/AP-2依赖性的突触结合蛋白内化，并将其靶向活神经元中的再循环小泡池。stonin 2促进突触结合蛋白内吞作用的能力取决于它与AP-2的结合、完整的μ-同源结构域以及功能性AP-2异源四聚体。我们的数据确定stonin 2是一种依赖AP-2的内吞分选衔接蛋白，用于突触结合蛋白的内化和再循环。
