Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells

Narasimha V. Hegde, Gordon Lee Jensen, Erica L. Unger

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)405-412
Number of pages8
JournalExperimental Cell Research
Volume317
Issue number4
DOIs
StatePublished - Feb 15 2011

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Dopamine Plasma Membrane Transport Proteins
RNA Stability
Endocytosis
Down-Regulation
Iron
Deferoxamine
Ubiquitination
Recycling
Post Translational Protein Processing
Neuroblastoma
Confocal Microscopy
Proteins
Phosphorylation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Hegde, Narasimha V. ; Jensen, Gordon Lee ; Unger, Erica L. / Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells. In: Experimental Cell Research. 2011 ; Vol. 317, No. 4. pp. 405-412.
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Iron chelation down-regulates dopamine transporter expression by decreasing mRNA stability and increasing endocytosis in N2a cells. / Hegde, Narasimha V.; Jensen, Gordon Lee; Unger, Erica L.

In: Experimental Cell Research, Vol. 317, No. 4, 15.02.2011, p. 405-412.

Research output: Contribution to journalArticle

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