Detection of novel intracellular alpha-synuclein oligomeric species by fluorescence lifetime imaging.
Oligomerization and aggregation of alpha-synuclein molecules are believed to play a major role in neuronal dysfunction and loss in Parkinson's disease (PD) and dementia with Lewy bodies. However, alpha-synuclein oligomerization and aggregation have been detected only indirectly in cells using detergent extraction methods. Here, we show for the first time ... intracellular alpha-synuclein oligomerization using fluorescence lifetime imaging (FLIM). Two forms of alpha-synuclein homomeric interactions were detected: an antiparallel amino terminus-carboxyl terminus interaction between alpha-synuclein molecules, and a close amino terminus-carboxy terminus interaction within single alpha-synuclein molecules. Coexpression of the chaperone protein Hsp70, which can block alpha-synuclein toxicity in several systems, causes alpha-synuclein to adopt a different, open conformation, but Hsp70 does not alter alpha-synuclein-alpha-synuclein interactions. Thus, the neuroprotective effect of Hsp70 can be explained by its chaperone activity on alpha-synuclein molecules, rather than alteration of alpha-synuclein-alpha-synuclein interactions.
Mesh Terms:
Cell Line, Tumor, Dimerization, Glioma, HSP70 Heat-Shock Proteins, Half-Life, Humans, Lasers, Microscopy, Fluorescence, Molecular Chaperones, Protein Binding, Protein Conformation, Transfection, alpha-Synuclein
Cell Line, Tumor, Dimerization, Glioma, HSP70 Heat-Shock Proteins, Half-Life, Humans, Lasers, Microscopy, Fluorescence, Molecular Chaperones, Protein Binding, Protein Conformation, Transfection, alpha-Synuclein
FASEB J.
Date: Oct. 01, 2006
PubMed ID: 17012257
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