Li Yuting, Schmidt-Edelkraut Udo, Poetz Fabian, Oliva Ilaria, Mandl Claudia, Hölzl-Wenig Gabriele, Schönig Kai, Bartsch Dusan, Ciccolini Francesca
From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg and.
the Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5 Mannheim, Germany.
J Biol Chem. 2015 Feb 13;290(7):4343-55. doi: 10.1074/jbc.M114.618686. Epub 2014 Dec 24.
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.
激活室管膜下区（SEZ）的γ-氨基丁酸A受体（GABA(A)Rs）可诱导前体细胞发生超极化和渗透性肿胀，从而促进表皮生长因子受体（EGFR）的表面表达并使细胞进入细胞周期。然而，GABA能调节细胞肿胀的潜在机制尚不清楚。在此，我们发现GABA(A)Rs与水通道水通道蛋白（AQP）4在出生后SEZ中富含prominin-1免疫阳性（P(+)）的前体细胞中共定位，这些前体细胞包括神经干细胞。GABA(A)R信号传导通过减少与水通道相关的丝氨酸磷酸化来促进AQP4的表达。GABA(A)R信号传导对AQP4表达的调节是其对细胞肿胀和EGFR表达产生影响的关键。此外，GABA(A)R功能还会影响神经前体细胞在体外和体内对渗透性刺激产生肿胀的能力。因此，GABA(A)Rs对AQP4的调节参与控制神经干细胞的激活以及SEZ中的水交换动力学。
