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- Title
Lipid Rafts Mediate the Synaptic Localization of α-Synuclein.
- Authors
Fortin, Doris L.; Troyer, Matthew D.; Nakamura, Ken; Kubo, Shin-ichiro; Anthony, Malcolm D.; Edwards, Robert H.
- Abstract
α-Synuclein contributes to the pathogenesis of Parldnson's disease (PD), but its precise role in the disorder and its normal function remain poorly understood. Consistent with a presumed role in neurotransmitter release and its prominent deposition in the dystrophic neurites of PD, &alpha-synuclein localizes almost exclusively to the nerve terminal. In brain extracts, however, α-synuclein behaves as a soluble, monomeric protein. Using a binding assay to characterize the association of &alpha-synuclein with cell membranes, we find that α-synuclein binds saturably and with high affinity to characteristic intracellular structures that double label for components of lipid rafts. Biochemical analysis demonstrates the interaction of α-synuclein with detergent-resistant membranes and reveals a shift in electrophoretic mobility of the raft-associated protein. In addition, the A30P mutation associated with PD disrupts the interaction of α-synuclein with lipid rafts. Furthermore, we find that both the A30P mutation and raft disruption redistribute α-synuclein away from synapses, indicating an important role for raft association in the normal function of α-synuclein and its role in the pathogenesis of PD.
- Subjects
NUCLEIN; PARKINSON'S disease; BRAIN diseases; CELL membranes; NEURAL circuitry
- Publication
Journal of Neuroscience, 2004, Vol 24, Issue 30, p6715
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.1594-04.2004