Role of complexin II in astrocytes

复杂蛋白是一类参与调节神经递质释放的细胞质蛋白。络合蛋白I被认为是抑制性突触的标记物，而络合蛋白II （Cpx II）主要标记兴奋性神经末梢。虽然神经递质释放发生在突触前末端，但最近的证据表明星形胶质细胞具有与突触囊泡释放相同的神经元机制。由于Cpx II是这种神经元机制的一个组成部分，我们计划研究它在这些胶质细胞释放谷氨酸中的作用。该研究项目将解决以下假设：1)Cpx II存在于星形胶质细胞中，并调节这些细胞的谷氨酸释放；2)Cpx II调节突触神经传递；3)氧化应激影响Cpx II介导的谷氨酸释放；4)Cpx II调节一种新的独特形式的星形胶质细胞谷氨酸释放，不同于病理条件下其他类型的谷氨酸释放。这些问题将通过星形胶质细胞和神经元的原代培养来解决，其中Cpx II基因表达的敲低将产生，Cpx II功能改变的相应基因组效应将在星形胶质细胞和神经元中随着能量代谢的变化而被确定。我们相信这个研究项目不仅会增加我们对复杂素在星形胶质细胞功能中的作用的理解，而且还会为这些细胞释放谷氨酸的意义、这一过程对兴奋性神经传递的影响及其在病理条件下的易感性提供新的见解。

Complexins constitute a family of cytosolic proteins that are involved in the regulation of neurotransmitter release. Complexin I is considered a marker of inhibitory synapses, while complexin II (Cpx II) labels predominantly excitatory nerve terminals. Although it is clear that neurotransmitter release occurs at the presynaptic terminal, recent evidence suggest that astrocytes possess the same neuronal machinery used for synaptic vesiclar release. Since Cpx II is an integral part of this neuronal machinery, we plan to study its role in the release of glutamate from these glial cells. The research project will address hypotheses that consider 1) Cpx II is present in astrocytes and regulates the release of glutamate from these cells, 2) Cpx II II modulates synaptic neurotransmission, 3) Oxidative stress influences Cpx II-mediated glutamate release, and 4) Cpx II regulates a novel and distinct form of astrocytic glutamate release that is different to other types of glutamate release operating under conditions of pathology. These issues will be addressed using primary cultures of astrocytes and neurons, in which knockdown of Cpx II gene expression will be produced and consequential genomic effects of altered Cpx II function will be identified in astrocytes and neurons along with energy metabolism changes. We are confident this research project will not only increase our understanding of the role of complexins in astrocyte function, but will also provide new insight into the significance of glutamate release from these cells, the influence of this process on excitatory neurotransmission, and its vulnerability under pathological conditions.