Lipid rafts mediate the synaptic localization of alpha-synuclein.
J Neurosci
; 24(30): 6715-23, 2004 Jul 28.
Article
en En
| MEDLINE
| ID: mdl-15282274
ABSTRACT
Alpha-synuclein contributes to the pathogenesis of Parkinson'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, alpha-synuclein behaves as a soluble, monomeric protein. Using a binding assay to characterize the association of alpha-synuclein with cell membranes, we find that alpha-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 alpha-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 alpha-synuclein with lipid rafts. Furthermore, we find that both the A30P mutation and raft disruption redistribute alpha-synuclein away from synapses, indicating an important role for raft association in the normal function of alpha-synuclein and its role in the pathogenesis of PD.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Lovastatina
/
Microdominios de Membrana
/
Proteínas del Tejido Nervioso
Idioma:
En
Revista:
J Neurosci
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos