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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Completion of neuronal migration regulated by loss of Ca2+ transients.
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Completion of neuronal migration regulated by loss of Ca2+ transients.

机译:神经元迁移的完成受Ca2 +瞬态损失的调节。

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The migration of immature neurons constitutes one of the major processes by which the central nervous system takes shape. Completing the migration at the final destination requires the loss of cell body motility, but little is known about the signaling mechanisms underlying this process. Here, we show that a loss of transient Ca(2+) elevations triggers the completion of cerebellar granule cell migration. Simultaneous observation of the intracellular Ca(2+) levels and cell movement in cerebellar slices of the early postnatal mice revealed that granule cells exhibit distinct frequencies of the transient Ca(2+) elevations as they migrate in different cortical layers, and complete the migration only after the loss of Ca(2+) elevations. The reduction of the Ca(2+) elevation frequency by decreasing Ca(2+) influx, or by inhibiting the activity of phospholipase C, PKC, or Ca(2+)/calmodulin, halted the granule cell movement prematurely. In contrast, increasing the Ca(2+) elevation frequency by increasing Ca(2+)release from internal stores, or by elevating intracellular cAMP levels, significantly delayed the completion of granule cell migration. The timing of the loss of Ca(2+) elevations was intrinsically set in the granule cells and influenced by external cues. These results suggest that Ca(2+) signaling, dictated by multiple signaling systems, functions as a mediator for completing the migration of immature neurons.
机译:未成熟神经元的迁移是中枢神经系统形成的主要过程之一。在最终目的地完成迁移需要丧失细胞的运动能力,但对该过程背后的信号传导机制知之甚少。在这里,我们表明,瞬时Ca(2+)升高的损失会触发小脑颗粒细胞迁移的完成。对早期产后小鼠小脑切片中细胞内Ca(2+)水平和细胞运动的同时观察显示,颗粒细胞在不同的皮质层中迁移时表现出不同的瞬时Ca(2+)升高频率,并完成迁移仅在失去Ca(2+)升高之后。通过减少Ca(2+)流入或通过抑制磷脂酶C,PKC或Ca(2 +)/钙调蛋白的活性来减少Ca(2+)升高的频率,过早地停止了颗粒细胞的运动。相反,通过增加内部存储中的Ca(2+)释放或通过提高细胞内cAMP水平来增加Ca(2+)升高频率,显着延迟了颗粒细胞迁移的完成。 Ca(2+)升高损失的时间是固有设置在颗粒细胞中,并受外部提示的影响。这些结果表明,Ca(2+)信号,由多个信号系统决定,起着完成未成熟神经元迁移的中介作用。

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