The clathrin-dependent localization of dopamine transporter to surface membranes is affected by α-synuclein.
J Mol Neurosci
; 52(2): 167-76, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24048740
Parkinson's disease (PD) is a progressive age-dependent neurodegenerative disorder, predominantly affecting the dopamine-producing neurons residing at the substantia nigra. Abnormalities in α-synuclein (α-Syn) and dopamine transporter (DAT) are implicated in the pathogenesis of PD. We tested the hypothesis that α-Syn regulates surface DAT localization and DAT activity, in cultured cells co-expressing α-Syn and DAT, and in brains of mice modeling PD, transgenic for the mutant A53T α-Syn form. The results indicate that α-Syn expression affects the partitioning of DAT between the cell surface and intracellular compartments, resulting in lower surface DAT levels. Accordingly, lower uptake of tritiated dopamine was measured in synaptosomes of A53T α-Syn transgenic mouse brains. Importantly, we show that the effect of α-Syn on surface DAT is mediated by clathrin. Downregulation of clathrin by specific siRNAs directed against its heavy chain abolished the effect of α-Syn on phorbol 12-myristate 13-acetate-induced DAT internalization. These results suggest that α-Syn plays a role in regulating dopamine homeostasis through its involvement in clathrin-mediated endocytosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Membrana Celular
/
Clatrina
/
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática
/
Alfa-Sinucleína
Límite:
Animals
Idioma:
En
Revista:
J Mol Neurosci
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Israel
Pais de publicación:
Estados Unidos