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- Title
Optical Reporters for the Conformation of α-Synuclein Reveal a Specific Interaction with Mitochondria.
- Authors
Nakamura, Ken; Nemani, Venu M.; Wallender, Erika K.; Kaehlcke, Katrin; Ott, Melanie; Edwards, Robert H.
- Abstract
The aggregation of abnormally folded proteins is a defining feature of neurodegenerative disease, but it has not previously been possible to assess the conformation of these proteins in a physiologically relevant context, before they form morphologically recognizable aggregates. We now describe FRET-based reporters for the conformation of α-synuclein, a protein central to the pathogenesis of Parkinson's disease (PD). Characterization in vitro shows that α-synuclein adopts a relatively "closed" conformation in solution that converts to "open" on membrane binding. In living cells, the closed conformation predominates. In neurons, however, cell bodies contain a much larger proportion of the open conformation than synaptic boutons. To account for these differences, we also used the reporters to characterize the interaction with native membranes.Wefind that the conformation of α-synuclein responds selectively to mitochondria, indicating a direct link between α-synuclein and an organelle strongly implicated in the pathogenesis of PD.
- Subjects
PROTEIN conformation; NEURODEGENERATION; MITOCHONDRIA; PARKINSON'S disease; DEGENERATION (Pathology); CARCINOGENESIS
- Publication
Journal of Neuroscience, 2008, Vol 28, Issue 47, p12305
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.3088-08.2008