Striedinger Katharine, Meda Paolo, Scemes Eliana
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York.
Glia. 2007 Apr 15;55(6):652-62. doi: 10.1002/glia.20494.
In the mature central nervous system (CNS) regulated secretion of ATP from astrocytes is thought to play a significant role in cell signaling. Whether such a mechanism is also operative in the developing nervous system and, if so, during which stage of development, has not been investigated. We have tackled this question using cells derived from reconstituted neurospheres, as well as brain explants of embryonic mice. Here, we show that in both models of neural cell development, astrocyte progenitors are competent for the regulated secretion of ATP-containing vesicles. We further document that this secretion is dependent on cytosolic Ca(2+) and the v-SNARE system, and takes place by exocytosis. Interference with ATP secretion alters spontaneous Ca(2+) oscillations and migration of neural progenitors. These data indicate that astrocyte progenitors acquire early in development the competence for regulated secretion of ATP, and that this event is implicated in the regulation of at least two cell functions, which are critical for the proper morphogenesis and functional maturation of the CNS.
在成熟的中枢神经系统（CNS）中，星形胶质细胞对ATP的调节性分泌被认为在细胞信号传导中发挥重要作用。这种机制在发育中的神经系统中是否也起作用，如果是，在发育的哪个阶段起作用，尚未得到研究。我们使用来自重组神经球的细胞以及胚胎小鼠的脑外植体来解决这个问题。在这里，我们表明，在神经细胞发育的两种模型中，星形胶质细胞祖细胞都具备调节性分泌含ATP囊泡的能力。我们进一步证明，这种分泌依赖于胞质Ca(2+)和v-SNARE系统，并通过胞吐作用发生。干扰ATP分泌会改变神经祖细胞的自发Ca(2+)振荡和迁移。这些数据表明，星形胶质细胞祖细胞在发育早期就获得了调节性分泌ATP的能力，并且这一事件与至少两种细胞功能的调节有关，而这两种细胞功能对于中枢神经系统的正常形态发生和功能成熟至关重要。
