Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
Elife. 2022 Jan 11;11:e71198. doi: 10.7554/eLife.71198.
Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Conflicting models have been proposed regarding the mechanisms of SV endocytosis, most notably clathrin/adaptor protein complex 2 (AP-2)-mediated endocytosis and clathrin-independent ultrafast endocytosis. Partitioning between these pathways has been suggested to be controlled by temperature and stimulus paradigm. We report on the comprehensive survey of six major SV proteins to show that SV endocytosis in mouse hippocampal neurons at physiological temperature occurs independent of clathrin while the endocytic retrieval of a subset of SV proteins including the vesicular transporters for glutamate and GABA depend on sorting by the clathrin adaptor AP-2. Our findings highlight a clathrin-independent role of the clathrin adaptor AP-2 in the endocytic retrieval of select SV cargos from the presynaptic cell surface and suggest a revised model for the endocytosis of SV membranes at mammalian central synapses.
神经递质传递基于突触小泡（SVs）的出胞融合，随后是内吞膜的回收和 SV 的再形成。关于 SV 内吞的机制，已经提出了相互矛盾的模型，主要是网格蛋白/衔接蛋白复合物 2（AP-2）介导的内吞作用和非网格蛋白依赖的超快内吞作用。有人提出，这些途径之间的分配受温度和刺激模式的控制。我们报告了对六种主要 SV 蛋白的全面调查，结果表明，在生理温度下，小鼠海马神经元中的 SV 内吞作用不依赖于网格蛋白，而包括谷氨酸和 GABA 囊泡转运体在内的一组 SV 蛋白的内吞回收依赖于网格蛋白衔接蛋白 AP-2 的分拣。我们的研究结果突出了网格蛋白衔接蛋白 AP-2 在从突触前细胞表面选择性 SV cargos 的内吞回收中的非网格蛋白依赖性作用，并为哺乳动物中枢突触 SV 膜的内吞作用提出了一个修正模型。
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