SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses
| Autor: | Tanja Maritzen, Stefan Markovic, Volker Haucke, Jens Dernedde, Figen Beceren-Braun, Dmytro Puchkov, Hartmut Oschkinat, Carsten C. Mahrenholz, Seong Joo Koo, Rudolf Volkmer |
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| Rok vydání: | 2011 |
| Předmět: |
Synaptobrevin
Endocytic cycle Hippocampus Synaptic Transmission Synaptic vesicle Clathrin Exocytosis Cell Line R-SNARE Proteins Mice Animals Humans Multidisciplinary clathrin-mediated endocytosis structure biology Biological Sciences Endocytosis Rats Cell biology Adaptor Proteins Vesicular Transport Protein Transport Monomeric Clathrin Assembly Proteins Synapses biology.protein Ap180 Soluble NSF attachment protein SNARE Proteins Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 108(33): 13540-13545 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Neurotransmission depends on the exo-endocytosis of synaptic vesicles at active zones. Synaptobrevin 2 [also known as vesicle-associated membrane protein 2 (VAMP2)], the most abundant synaptic vesicle protein and a major soluble NSF attachment protein receptor (SNARE) component, is required for fast calcium-triggered synaptic vesicle fusion. In contrast to the extensive knowledge about the mechanism of SNARE-mediated exocytosis, little is known about the endocytic sorting of synaptobrevin 2. Here we show that synaptobrevin 2 sorting involves determinants within its SNARE motif that are recognized by the ANTH domains of the endocytic adaptors AP180 and clathrin assembly lymphoid myeloid leukemia (CALM). Depletion of CALM or AP180 causes selective surface accumulation of synaptobrevin 2 but not vGLUT1 at the neuronal surface. Endocytic sorting of synaptobrevin 2 is mediated by direct interaction of the ANTH domain of the related endocytic adaptors CALM and AP180 with the N-terminal half of the SNARE motif centered around M46, as evidenced by NMR spectroscopy analysis and site-directed mutagenesis. Our data unravel a unique mechanism of SNARE motif-dependent endocytic sorting and identify the ANTH domain proteins AP180 and CALM as cargo-specific adaptors for synaptobrevin endocytosis. Defective SNARE endocytosis may also underlie the association of CALM and AP180 with neurodevelopmental and cognitive defects or neurodegenerative disorders. |
| Databáze: | OpenAIRE |
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