Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells.
Exp Cell Res
; 317(4): 405-12, 2011 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-21147099
ABSTRACT
Cell surface expression of the dopamine transporter (DAT) is determined by the relative rates of its internalization and recycling. Changes in the cellular labile iron pool (LIP) affect many cellular mechanisms including those that regulate DAT trafficking. In this study, we analyzed DAT expression and posttranslational modifications in response to changes in cellular iron in transfected neuroblastoma cells (N2a). Iron chelation by desferrioxamine (DFO) altered DAT protein levels by decreasing the stability of DAT mRNA. Increased phosphorylation and ubiquitination of this transporter protein following DFO treatment were also observed. Cellular iron depletion elevated protein levels of the early endosomal marker Rab5. Moreover, confocal microscopy studies showed increased localization of DAT into the endosomal compartment in DFO-treated cells compared to control. Together, these findings suggest that cellular iron depletion regulates DAT expression through reducing mRNA stability as well as an increasing in endocytosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quelantes de Ferro
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Estabilidade de RNA
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Endocitose
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Proteínas da Membrana Plasmática de Transporte de Dopamina
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Ferro
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article