摘要：

Astrocytes, a subtype of glial cells in the central nervous system, have for years been treated as mere support cells. Recent studies have revealed their regulatory role in synaptic transmission and plasticity. One of the most important features astrocytes exhibit is a Ca-dependent glutamate release, which is believed to mediate astrocyte-to-neuron signaling. One of the mechanisms that have been postulated is regulated exocytosis triggered by elevation of cytosolic Caconcentration. However, the lack of knowledge of exocytosis machinery, and especially the identity of the Ca-sensor in astrocytes, has called this hypothesis into question. ^ Here, I combine molecular biology with fluorescent microscopy techniques to identify a set of vesicular proteins essential for the Ca-evoked exocytosis of glutamate and to characterize their functions in astrocytes. First, I find evidence that vesicular glutamate transporters and membrane proteins crucial for evoked exocytosis are present in astrocytes. Second, I successfully inhibit astrocytic glutamate release by over-expressing a dominant-negative inhibitor of evoked exocytosis. Third, I screen all known members of the synaptotagmin family that are enriched in brain, and identify that synaptotagmin IV as the Casensor for the Ca-dependent release of glutamate from astrocytes. ^ These findings offer important information for understanding the mechanism of glutamate-mediated astrocyte-to-neuron signaling, which sets the stage for future investigation of the physiological and pathological roles of astrocytes in our central nervous system. ^

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