title: Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells.
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.
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA. nvh1@psu.edu
authors.forename: Narasimha V
authors.initials: NV
authors.lastname: Hegde
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Jensen
authors.forename: Erica L
authors.initials: EL
authors.lastname: Unger
mesh_terms: D045744:Cell Line, Tumor; D003676:Deferoxamine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004705:Endocytosis / Q000187:drug effects*; D011992:Endosomes; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000502:physiology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D009447:Neuroblastoma; D020871:RNA Stability / Q000187:drug effects*; D014162:Transfection
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine