Density of GM1 in Nanoclusters Is a Critical Factor in the Formation of a Spherical Assembly of Amyloid 尾-Protein on Synaptic Plasma Membranes

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• 作者：Teruhiko Matsubara ; Kazutoshi Iijima ; Naoki Yamamoto ; Katsuhiko Yanagisawa ; Toshinori Sato
• 刊名：Langmuir
• 出版年：2013
• 出版时间：February 19, 2013
• 年：2013
• 卷：29
• 期：7
• 页码：2258-2264
• 全文大小：366K
• 年卷期：v.29,no.7(February 19, 2013)
• ISSN：1520-5827

文摘

The deposition of amyloid 尾-protein (A尾) is a pathological hallmark of Alzheimer鈥檚 disease (AD). We previously found that the ganglioside-enriched microdomains (ganglioside clusters) in presynaptic neuronal membranes play a key role in the initiation of the A尾 assembly process. However, not all ganglioside clusters accelerate A尾 assembly. In the present study, we directly observed a spherical A尾 in an atomic force microscopic study on the morphology of a reconstituted lipid bilayer composed of lipids that were extracted from a detergent-resistant membrane microdomain (DRM) fraction of synaptosomes prepared from aged mouse brain. The A尾 assembly was generated on a distinctive GM1 domain, which was characterized as the A尾-sensitive ganglioside nanocluster (ASIGN). By using an artificial GM1 cluster-binding peptide, ASIGN was found to have a high density of GM1; therefore, there would be a critical density of GM1 in nanoclusters to induce A尾 binding and assembly. These results suggest that ganglioside-bound A尾 (GA尾), which acts as an endogenous seed for A尾 fibril formation in AD brains, is generated on ASIGN on synaptosomal membranes.