AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells

被引：129

作者：

Kong, Hui ^{[1
]}

Fan, Yi ^{[1
]}

Xie, Juan ^{[1
]}

Ding, Jianhua ^{[1
]}

Sha, Luolin ^{[1
]}

Shi, Xueru ^{[1
]}

Sun, Xiulan ^{[1
]}

Hu, Gang ^{[1
]}

机构：

[1] Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, Nanjing 210029, Jiangsu, Peoples R China

来源：

JOURNAL OF CELL SCIENCE | 2008年 / 121卷 / 24期

基金：

中国国家自然科学基金;

关键词：

Aquaporin-4; Adult neural stem cells; Calcium oscillations; Connexin43; L-type calcium channel;

D O I：

10.1242/jcs.035758

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aquaporin-4 (AQP4), a key molecule for maintaining water and ion homeostasis in the central nervous system, is expressed in adult neural stem cells (ANSCs) as well as astrocytes. However, little is known about the functions of AQP4 in the ANSCs in vitro. Here we show that AQP4 knockout inhibits the proliferation, survival, migration and neuronal differentiation of ANSCs derived from the subventricular zone of adult mice. Flow cytometric cell cycle analysis revealed that AQP4 knockout increased the basal apoptosis and induced a G2-M arrest in ANSCs. Using Fluo-3 Ca2+ imaging, we show that AQP4 knockout alters the spontaneous Ca2+ oscillations by frequency enhancement and amplitude suppression, and suppresses KCl-induced Ca2+ influx. AQP4 knockout downregulated the expression of connexin43 and the L-type voltage-gated Ca2+ channel CaV1.2 subtype in ANSCs. Together, these findings suggest that AQP4 plays a crucial role in regulating the proliferation, migration and differentiation of ANSCs, and this function of AQP4 is probably mediated by its action on intracellular Ca2+ dynamics.

引用

页码：4029 / 4036

页数：8

共 82 条

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