PMID- 23999124 OWN - NLM STAT- MEDLINE DCOM- 20140619 LR - 20211021 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 253 DP - 2013 Dec 3 TI - PKA modulates iron trafficking in the striatum via small GTPase, Rhes. PG - 214-20 LID - 10.1016/j.neuroscience.2013.08.043 [doi] AB - Ras homolog enriched in striatum (Rhes), is a highly conserved small guanosine-5'-triphosphate (GTP) binding protein belonging to the Ras superfamily. Rhes is involved in the dopamine receptor-mediated signaling and behavior though adenylyl cyclase. The striatum-specific GTPase share a close homology with Dexras1, which regulates iron trafficking in the neurons when activated though the post-translational modification called s-nitrosylation by nitric oxide (NO). We report that Rhes physiologically interacted with Peripheral benzodiazepine receptor-associated protein7 and participated in iron uptake via divalent metal transporter 1 similar to Dexras1. Interestingly, Rhes is not S-nitrosylated by NO-treatment, however phosphorylated by protein kinase A at the site of serine-239. Two Rhes mutants - the phosphomimetic form (serine 239 to aspartic acid) and constitutively active form (alanine 173 to valine) - displayed an increase in iron uptake compared to the wild-type Rhes. These findings suggest that Rhes may play a crucial role in striatal iron homeostasis. CI - Copyright (c) 2013 IBRO. All rights reserved. FAU - Choi, Bo-Ran AU - Choi BR AD - Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, The Perlman School of Medicine at the University of Pennsylvania, 125 S 31 St. TRL Rm 2207, Philadelphia, PA 19104. FAU - Bang, Sookhee AU - Bang S AD - Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, The Perlman School of Medicine at the University of Pennsylvania, 125 S 31 St. TRL Rm 2207, Philadelphia, PA 19104. FAU - Chen, Yong AU - Chen Y AD - Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, The Perlman School of Medicine at the University of Pennsylvania, 125 S 31 St. TRL Rm 2207, Philadelphia, PA 19104. FAU - Cheah, Jaime H AU - Cheah JH AD - Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, The Perlman School of Medicine at the University of Pennsylvania, 125 S 31 St. TRL Rm 2207, Philadelphia, PA 19104. FAU - Kim, Sangwon F AU - Kim SF AD - Department of Psychiatry and Pharmacology, Center for Neurobiology and Behavior, The Perlman School of Medicine at the University of Pennsylvania, 125 S 31 St. TRL Rm 2207, Philadelphia, PA 19104. LA - eng GR - DK084336/DK/NIDDK NIH HHS/United States GR - P30 HD026979/HD/NICHD NIH HHS/United States GR - HD026979/HD/NICHD NIH HHS/United States GR - R01 DK084336/DK/NIDDK NIH HHS/United States GR - MH079614/MH/NIMH NIH HHS/United States GR - R00 MH079614/MH/NIMH NIH HHS/United States GR - K99 MH079614/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130830 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (ACBD3 protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cation Transport Proteins) RN - 0 (Ferric Compounds) RN - 0 (Iron-Regulatory Proteins) RN - 0 (Membrane Proteins) RN - 0 (Quaternary Ammonium Compounds) RN - 0 (Siderophores) RN - 0 (solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 452VLY9402 (Serine) RN - E1UOL152H7 (Iron) RN - EC 2.5.1.18 (Glutathione Transferase) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 3.6.1.- (RASD2 protein, human) RN - J06Y7MXW4D (Deferoxamine) RN - UVP74NG1C5 (ferric ammonium citrate) SB - IM MH - Adaptor Proteins, Signal Transducing/metabolism MH - Animals MH - Biological Transport/drug effects/genetics MH - Cation Transport Proteins/metabolism MH - Cyclic AMP-Dependent Protein Kinases/*metabolism MH - Deferoxamine/pharmacology MH - Ferric Compounds/pharmacology MH - GTP-Binding Proteins/genetics/*metabolism MH - Glutathione Transferase/metabolism MH - Green Fluorescent Proteins/genetics/metabolism MH - HEK293 Cells MH - Humans MH - Immunoprecipitation MH - Iron/*metabolism MH - Iron-Regulatory Proteins/genetics/metabolism MH - Membrane Proteins/metabolism MH - Mutation/*genetics MH - Phosphorylation/drug effects/genetics MH - Quaternary Ammonium Compounds/pharmacology MH - Serine/metabolism MH - Siderophores/pharmacology MH - Transfection PMC - PMC3871862 MID - NIHMS521701 OTO - NOTNLM OT - A173V OT - DMT1 OT - EDTA OT - G protein OT - G31V OT - GEF OT - GST OT - GTP OT - HRP OT - IRE OT - NTBI OT - PAP7 OT - PBS OT - PKA OT - Rhes OT - S239A OT - S239D OT - Tf OT - TfR OT - alanine-173 valine OT - divalent metal transporter 1 OT - ethylenediaminetetraacetic acid OT - glutathione S-transferase OT - glycine-31 valine OT - guanidine exchange factor OT - guanosine-5'-triphosphate OT - horseradish peroxidase OT - iron uptake OT - iron-responsive element OT - nNOS OT - neuronal nitric oxide synthase, NO, nitric oxide OT - non-transferrin-bound iron OT - peripheral benzodiazepine receptor-associated protein7 OT - phosphate-buffered saline OT - phosphorylation OT - protein kinase A OT - ras homolog enriched in striatum OT - serine-239 alanine OT - serine-239 aspartic acid OT - striatum OT - transferrin OT - transferrin receptor OT - lambda PPase OT - lambda phosphatase EDAT- 2013/09/04 06:00 MHDA- 2014/06/20 06:00 PMCR- 2014/12/03 CRDT- 2013/09/04 06:00 PHST- 2013/07/11 00:00 [received] PHST- 2013/08/20 00:00 [revised] PHST- 2013/08/22 00:00 [accepted] PHST- 2013/09/04 06:00 [entrez] PHST- 2013/09/04 06:00 [pubmed] PHST- 2014/06/20 06:00 [medline] PHST- 2014/12/03 00:00 [pmc-release] AID - S0306-4522(13)00731-8 [pii] AID - 10.1016/j.neuroscience.2013.08.043 [doi] PST - ppublish SO - Neuroscience. 2013 Dec 3;253:214-20. doi: 10.1016/j.neuroscience.2013.08.043. Epub 2013 Aug 30.