First Author | Burré J | Year | 2010 |
Journal | Science | Volume | 329 |
Issue | 5999 | Pages | 1663-7 |
PubMed ID | 20798282 | Mgi Jnum | J:164218 |
Mgi Id | MGI:4830915 | Doi | 10.1126/science.1195227 |
Citation | Burre J, et al. (2010) Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329(5999):1663-7 |
abstractText | Presynaptic nerve terminals release neurotransmitters repeatedly, often at high frequency, and in relative isolation from neuronal cell bodies. Repeated release requires cycles of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-complex assembly and disassembly, with continuous generation of reactive SNARE-protein intermediates. Although many forms of neurodegeneration initiate presynaptically, only few pathogenic mechanisms are known, and the functions of presynaptic proteins linked to neurodegeneration, such as alpha-synuclein, remain unclear. Here, we show that maintenance of continuous presynaptic SNARE-complex assembly required a nonclassical chaperone activity mediated by synucleins. Specifically, alpha-synuclein directly bound to the SNARE-protein synaptobrevin-2/vesicle-associated membrane protein 2 (VAMP2) and promoted SNARE-complex assembly. Moreover, triple-knockout mice lacking synucleins developed age-dependent neurological impairments, exhibited decreased SNARE-complex assembly, and died prematurely. Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging. |