PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation

Yong Chen, Lauren Mathias, Juliana M. Falero-Perez, Sangwon F. Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Dexras1 is a small GTPase and plays a central role in neuronal iron trafficking. We have shown that stimulation of glutamate receptors activates neuronal nitric oxide synthase, leading to S-nitrosylation of Dexras1 and a physiological increase in iron uptake. Here we report that Dexras1 is phosphorylated by protein kinase A (PKA) on serine 253, leading to a suppression of iron influx. These effects were directly associated with the levels of S-nitrosylated Dexras1, whereby PKA activation reduced Dexras1 S-nitrosylation in a dose dependent manner. Moreover, we found that adiponectin modulates Dexras1 via PKA. Hence these findings suggest the involvement of the PKA pathway in modulating glutamate-mediated ROS in neurons, and hint to a functional crosstalk between S-nitrosylation and phosphorylation.

Original languageEnglish (US)
Article number37351
Pages (from-to)3212-3219
Number of pages8
JournalFEBS Letters
Volume589
Issue number20
DOIs
StatePublished - Oct 7 2015
Externally publishedYes

Keywords

  • Iron
  • Neuron
  • Nitric oxide
  • Phosphorylation
  • Post-translational modification
  • S-nitrosylation

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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