Amyloid-β Oligomers May Impair SNARE-Mediated Exocytosis by Direct Binding to Syntaxin 1a
| Autor: | Sejin Lee, Hye Yun Kim, Hyewhon Rhim, Yoosoo Yang, Jaewook Kim, Nayeon Ryoo, Yeon-Kyun Shin, Young-Soo Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Amyloid beta-Peptides
STX1A Brain Syntaxin 1 Munc-18 Neurotransmission Biology General Biochemistry Genetics and Molecular Biology Syntaxin 3 Exocytosis Article 3. Good health Cell biology Mice lcsh:Biology (General) Animals Protein Multimerization biological phenomena cell phenomena and immunity SNARE complex lcsh:QH301-705.5 SNARE complex assembly Protein Binding |
| Zdroj: | Cell Reports, Vol 12, Iss 8, Pp 1244-1251 (2015) CELL REPORTS(12): 8 |
| ISSN: | 2211-1247 |
| Popis: | Alzheimer's disease (AD) is closely associated with synaptic dysfunction, and thus current treatments often aim to stimulate neurotransmission to improve cognitive impairment. Whereas the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is essential for synaptic transmission, the correlation between SNAREs and AD neuropathology is unknown. Here, we report that intracellular amyloid-beta (A beta) oligomers directly inhibit SNARE-mediated exocytosis by impairing SNARE complex formation. We observe abnormal reduction of SNARE complex levels in the brains of APP/PS1 transgenic (TG) mice compared to age-matched wild-types. We demonstrate that A beta oligomers block SNARE complex assembly through the direct interaction with a target membrane (t)-SNARE syntaxin 1a in vitro. Furthermore, the results of the in vitro single-vesicle content-mixing assay reveal that A beta oligomers inhibit SNARE-mediated fusion pores. Thus, our study identifies a potential molecular mechanism by which intracellular A beta oligomers hamper SNARE-mediated exocytosis, likely leading to AD-associated synaptic dysfunctions. |
| Databáze: | OpenAIRE |
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