title: Neurturin evokes MAPK-dependent upregulation of Egr4 and KCC2 in developing neurons.
abstract: The K-Cl cotransporter KCC2 plays a crucial role in the functional development of GABA(A)-mediated responses rendering GABA hyperpolarizing in adult neurons. We have previously shown that BDNF upregulates KCC2 in immature neurons through the transcription factor Egr4. The effect of BDNF on Egr4 and KCC2 was shown to be dependent on the activation of ERK1/2. Here we demonstrate that the trophic factor neurturin can also trigger Egr4 expression and upregulate KCC2 in an ERK1/2-dependent manner. These results show that Egr4 is an important component in the mechanism for trophic factor-mediated upregulation of KCC2 in immature neurons involving the activation of specific intracellular pathways common to BDNF and Neurturin.
authors.affiliation: Neuroscience Center, University of Helsinki, Viikinkaari 4, 00014 Helsinki, Finland.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ludwig
authors.forename: Pavel
authors.initials: P
authors.lastname: Uvarov
authors.forename: Christophe
authors.initials: C
authors.lastname: Pellegrino
authors.forename: Judith
authors.initials: J
authors.lastname: Thomas-Crusells
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schuchmann
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
authors.forename: Matti S
authors.initials: MS
authors.lastname: Airaksinen
authors.forename: Claudio
authors.initials: C
authors.lastname: Rivera
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051765:Early Growth Response Transcription Factors / Q000096:biosynthesis* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D051101:Neurturin / Q000502:physiology*; D009924:Organ Culture Techniques; D027981:Symporters / Q000096:biosynthesis* / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*; D000096922:K Cl- Cotransporters
chemical_list: D051765:Early Growth Response Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D051101:Neurturin; D027981:Symporters; D000096922:K Cl- Cotransporters; C486392:Egr4 protein, mouse