title: Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.
abstract: Dorsal root ganglia (DRGs) contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury.
authors.affiliation: INSERM U1051, Institut des Neurosciences de Montpellier, Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ventéo
authors.forename: Steeve
authors.initials: S
authors.lastname: Bourane
authors.forename: Ilana
authors.initials: I
authors.lastname: Méchaly
authors.forename: Chamroeun
authors.initials: C
authors.lastname: Sar
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel Samad
authors.forename: Sylvie
authors.initials: S
authors.lastname: Puech
authors.forename: Rhoda
authors.initials: R
authors.lastname: Blostein
authors.forename: Jean
authors.initials: J
authors.lastname: Valmier
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pattyn
authors.forename: Patrick
authors.initials: P
authors.lastname: Carroll
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019771:Axotomy; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D008024:Ligands; D008465:Mechanoreceptors / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000201:enzymology / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008024:Ligands; D010455:Peptides; D021122:Protein Subunits; D012333:RNA, Messenger; C493726:Runx1 protein, mouse; D051096:Proto-Oncogene Proteins c-ret; D020813:Receptor, trkB; C498816:Fxyd2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase