title: γ-Aminobutyric A receptor (GABA(A)R) regulates aquaporin 4 expression in the subependymal zone: relevance to neural precursors and water exchange.
abstract: Activation of γ-aminobutyric A receptors (GABA(A)Rs) in the subependymal zone (SEZ) induces hyperpolarization and osmotic swelling in precursors, thereby promoting surface expression of the epidermal growth factor receptor (EGFR) and cell cycle entry. However, the mechanisms underlying the GABAergic modulation of cell swelling are unclear. Here, we show that GABA(A)Rs colocalize with the water channel aquaporin (AQP) 4 in prominin-1 immunopositive (P(+)) precursors in the postnatal SEZ, which include neural stem cells. GABA(A)R signaling promotes AQP4 expression by decreasing serine phosphorylation associated with the water channel. The modulation of AQP4 expression by GABA(A)R signaling is key to its effect on cell swelling and EGFR expression. In addition, GABA(A)R function also affects the ability of neural precursors to swell in response to an osmotic challenge in vitro and in vivo. Thus, the regulation of AQP4 by GABA(A)Rs is involved in controlling activation of neural stem cells and water exchange dynamics in the SEZ.
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
authors.forename: Udo
authors.initials: U
authors.lastname: Schmidt-Edelkraut
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
authors.forename: Fabian
authors.initials: F
authors.lastname: Poetz
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Oliva
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mandl
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hölzl-Wenig
authors.affiliation: the Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5 Mannheim, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schönig
authors.affiliation: the Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5 Mannheim, Germany.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bartsch
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and Ciccolini@nbio.uni-heidelberg.de.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ciccolini
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000502:physiology*; D015153:Blotting, Western; D048429:Cell Size; D002478:Cells, Cultured; D004805:Ependyma / Q000166:cytology / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009997:Osmotic Pressure; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014867:Water / Q000378:metabolism*
chemical_list: D051401:Aquaporin 4; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014867:Water; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: AQP4, EGFR, Osmotic Swelling, Prominin-1, Neural Stem Cells; Aquaporin; Epidermal Growth Factor Receptor (EGFR); GABA Receptor; GABA, AQP4, EGFR, Osmotic Swelling, Prominin-1, Neural Stem Cells; Neural Stem Cell (NSC); Water Channel