Density of GM1 in nanoclusters is a critical factor in the formation of a spherical assembly of amyloid β-protein on synaptic plasma membranes

Teruhiko Matsubara, Kazutoshi Iijima, Naoki Yamamoto, Katsuhiko Yanagisawa, Toshinori Sato

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The deposition of amyloid β-protein (Aβ) is a pathological hallmark of Alzheimer's 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 Aβ assembly process. However, not all ganglioside clusters accelerate Aβ assembly. In the present study, we directly observed a spherical Aβ 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 Aβ assembly was generated on a distinctive GM1 domain, which was characterized as the Aβ-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 Aβ binding and assembly. These results suggest that ganglioside-bound Aβ (GAβ), which acts as an endogenous seed for Aβ fibril formation in AD brains, is generated on ASIGN on synaptosomal membranes.

Original languageEnglish
Pages (from-to)2258-2264
Number of pages7
JournalLangmuir
Volume29
Issue number7
DOIs
Publication statusPublished - 2013 Feb 19

Fingerprint

Amyloidogenic Proteins
Gangliosides
Nanoclusters
Cell membranes
nanoclusters
assembly
membranes
proteins
Membranes
brain
lipids
Brain
Lipid bilayers
detergents
Detergents
Lipids
Peptides
peptides
mice
seeds

ASJC Scopus subject areas

  • Electrochemistry
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Materials Science(all)
  • Spectroscopy

Cite this

Density of GM1 in nanoclusters is a critical factor in the formation of a spherical assembly of amyloid β-protein on synaptic plasma membranes. / Matsubara, Teruhiko; Iijima, Kazutoshi; Yamamoto, Naoki; Yanagisawa, Katsuhiko; Sato, Toshinori.

In: Langmuir, Vol. 29, No. 7, 19.02.2013, p. 2258-2264.

Research output: Contribution to journalArticle

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