Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses

eLife

Pornparn Kongpracha¹  Shushi Nagamori¹  Koh-ichiro Takenaka²  Yasunori Mori²  Shigeo Takamori²  Tania López-Hernández³  Volker Haucke³ 

[1] Department of Laboratory Medicine, The Jikei University School of Medicine, Tokyo, Japan;Laboratory of Neural Membrane Biology, Graduate School of Brain Science, Doshisha University, Kyoto, Japan;Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany;

关键词: synapse;    endocytosis;    clathrin;    AP-2;    pHluorin;    Mouse;   

DOI  :  10.7554/eLife.71198

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY