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

Authors
 Keun Jae Ahn  ;  Seung R. Paik  ;  Kwang Chul Chung  ;  Jongsun Kim 
Citation
 Journal of Neurochemistry, Vol.97(1) : 265-279, 2006 
Journal Title
 Journal of Neurochemistry 
ISSN
 0022-3042 
Issue Date
2006
MeSH
Amino Acid Motifs/physiology ; Amino Acid Sequence/physiology ; Animals ; Brain/metabolism* ; CHO Cells ; Cell Membrane/metabolism* ; Cell Membrane Permeability/physiology ; Cricetinae ; Endocytosis/physiology* ; Humans ; K562 Cells ; Membrane Proteins/metabolism* ; Neurons/metabolism* ; Peptides/chemistry ; Peptides/metabolism ; Protein Structure, Tertiary/physiology ; Protein Transport/physiology ; Temperature ; alpha-Synuclein/chemistry ; alpha-Synuclein/metabolism* ; beta-Synuclein/metabolism ; gamma-Synuclein/metabolism
Keywords
α‐synuclein membrane translocation ; Parkinson's disease ; protein transduction domain ; repeat sequence
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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2006.03731.x/abstract
DOI
10.1111/j.1471-4159.2006.03731.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
Ahn, Keun Jae(안근재)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108770
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