Kastning Kathrin, Kukhtina Viktoria, Kittler Josef T, Chen Guojun, Pechstein Arndt, Enders Sven, Lee Sang Hyoung, Sheng Morgan, Yan Zhen, Haucke Volker
Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2991-6. doi: 10.1073/pnas.0611170104. Epub 2007 Feb 8.
alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors undergo constitutive and ligand-induced internalization that requires dynamin and the clathrin adaptor complex AP-2. We report here that an atypical basic motif within the cytoplasmic tails of AMPA-type glutamate receptors directly associates with mu2-adaptin by a mechanism similar to the recognition of the presynaptic vesicle protein synaptotagmin 1 by AP-2. A synaptotagmin 1-derived AP-2 binding peptide competes the interaction of the AMPA receptor subunit GluR2 with AP-2mu and increases the number of surface active glutamate receptors in living neurons. Moreover, fusion of the GluR2-derived tail peptide with a synaptotagmin 1 truncation mutant restores clathrin/AP-2-dependent internalization of the chimeric reporter protein. These data suggest that common mechanisms regulate AP-2-dependent internalization of pre- and postsynaptic membrane proteins.
α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）型谷氨酸受体经历组成型和配体诱导的内吞作用，这一过程需要发动蛋白和网格蛋白衔接复合体AP-2。我们在此报告，AMPA型谷氨酸受体胞质尾内的一个非典型碱性基序通过一种类似于AP-2识别突触前囊泡蛋白突触结合蛋白1的机制，直接与μ2-衔接蛋白结合。一个源自突触结合蛋白1的AP-2结合肽能够竞争AMPA受体亚基GluR2与AP-2μ的相互作用，并增加活神经元中表面活性谷氨酸受体的数量。此外，将源自GluR2的尾肽与突触结合蛋白1截短突变体融合，可恢复网格蛋白/AP-2依赖的嵌合报告蛋白的内吞作用。这些数据表明，共同的机制调节突触前和突触后膜蛋白的AP-2依赖的内吞作用。
