Amino acid sequence motifs and mechanistic features of the membrane translocation of α-synuclein

Keun Jae Ahn, Seung R. Paik, Kwang Chul Chung, Jongsun Kim

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77 Citations (Scopus)

Abstract

Many lines of evidence suggest that α-synuclein can be secreted from cells and can penetrate into them, although the detailed mechanism is not known. In this study, we investigated the amino acid sequence motifs required for the membrane translocation of α-synuclein, and the mechanistic features of the phenomenon. We first showed that not only α-synuclein but also β- and γ-synucleins penetrated into live cells, indicating that the conserved N-terminal region might be responsible for the membrane translocation. Using a series of deletion mutants, we demonstrated that the 11-amino acid imperfect repeats found in synuclein family members play a critical role in the membrane translocation of these proteins. We further demonstrated that fusion peptides containing the 11-amino acid imperfect repeats of α-synuclein can transverse the plasma membrane, and that the membrane translocation efficiency is optimal when the peptide contains two repeat motifs. α-Synuclein appeared to be imported rapidly and efficiently into cells, with detectable protein in the cytoplasm within 5 min after exogenous treatment. Interestingly, the import of α-synuclein at 4°C was comparable with the import observed at 37°C. Furthermore, membrane translocation of α-synuclein was not significantly affected by treatment with inhibitors of endocytosis. These results suggest that the internalization of α-synuclein is temperature-insensitive and occurs very rapidly via a mechanism distinct from normal endocytosis.

Original languageEnglish
Pages (from-to)265-279
Number of pages15
JournalJournal of Neurochemistry
Volume97
Issue number1
DOIs
Publication statusPublished - 2006 Apr

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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