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

被引:15
作者
Chen, Yong [1 ]
Mathias, Lauren [1 ]
Falero-Perez, Juliana M. [1 ]
Kim, Sangwon F. [1 ]
机构
[1] Univ Penn, Perlman Sch Med, Dept Psychiat & Syst Pharmacol & Translat Therape, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA
关键词
Iron; Nitric oxide; S-nitrosylation; Phosphorylation; Neuron; Post-translational modification; NITRIC-OXIDE SYNTHASE; ADIPOCYTE HORMONE ADIPONECTIN; ALPHA-ASSOCIATED PROTEIN; POSTTRANSLATIONAL MODIFICATIONS; REGULATORY PROTEIN-2; SMALL GTPASE; CELL-DEATH; RECEPTOR; EXPRESSION; NEURONS;
D O I
10.1016/j.febslet.2015.08.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (PICA) on serine 253, leading to a suppression of iron influx. These effects were directly associated with the levels of S-nitrosylated Dexras1, whereby PICA activation reduced Dexras1 S-nitrosylation in a dose dependent manner. Moreover, we found that adiponectin modulates Dexras1 via PICA. Hence these findings suggest the involvement of the PICA pathway in modulating glutamate-mediated ROS in neurons, and hint to a functional crosstalk between S-nitrosylation and phosphorylation. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3212 / 3219
页数:8
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