title: Rab7-a novel redox target that modulates inflammatory pain processing.
abstract: Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.
authors.affiliation: Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.|Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kallenborn-Gerhardt
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Christine V
authors.initials: CV
authors.lastname: Möser
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Jana E
authors.initials: JE
authors.lastname: Lorenz
authors.affiliation: Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany.
authors.forename: Mirco
authors.initials: M
authors.lastname: Steger
authors.affiliation: Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Heidler
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Reynir
authors.initials: R
authors.lastname: Scheving
authors.affiliation: Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.|Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Kennel
authors.affiliation: Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Flauaus
authors.affiliation: Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.|Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Lu
authors.affiliation: Developmental and Cell Biology, University of California, Irvine, CA, USA.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Edinger
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Tegeder
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Frankfurt am Main, Germany.|Fraunhofer Institute for Molecular Biology and Applied Ecology-Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Heide
authors.affiliation: Functional Proteomics, SFB815 Core Unit, Goethe University, Frankfurt am Main, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.affiliation: Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.|Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Schmidtko
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010146:Pain / Q000378:metabolism*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D017382:Reactive Oxygen Species; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; D020691:rab GTP-Binding Proteins