AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells
AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells
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AQP4敲除损害成体神经干细胞的增殖、迁移和神经元分化
DOI：
10.1242/jcs.035758
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发表时间：
2008-12-15
影响因子：
4
通讯作者：
Hu, Gang
中科院分区：
文献类型：
--
作者：
Kong, Hui;Fan, Yi;Hu, Gang
水通道蛋白-4（AQP 4）是维持中枢神经系统水和离子稳态的关键分子，在成体神经干细胞（ANSC）和星形胶质细胞中表达。然而，关于AQP 4在体外ANSC中的功能知之甚少。在这里，我们表明，AQP 4基因敲除抑制成年小鼠室管膜下区来源的ANSC的增殖，存活，迁移和神经元分化。流式细胞仪细胞周期分析显示，AQP 4基因敲除增加了ANSC的基础凋亡，并诱导了G2-M期阻滞。利用Fluo-3 Ca 2+成像，我们发现AQP 4敲除通过频率增强和幅度抑制改变了自发Ca 2+振荡，并抑制KCl诱导的Ca 2+内流。AQP 4基因敲除可下调ANSC中Cx43和L型电压门控钙通道CaV1.2亚型的表达。总之，这些研究结果表明，AQP 4在调节ANSC的增殖，迁移和分化中起着至关重要的作用，AQP 4的这种功能可能是通过其对细胞内Ca 2+动力学的作用介导的。
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.