Homeostatic Synaptic Depression

描述（由申请人提供）：越来越多的证据表明，在从果蝇到小鼠和人类的生物体中，神经功能通过稳态信号系统稳定。在每个实施例中，在神经元或肌肉兴奋性的实验扰动之后鉴定稳态信号传导系统。在每个实验中，细胞通过调节离子通道丰度或突触传递来响应实验扰动，以抵消扰动并重新建立正常的活性水平。现在广泛假设，有缺陷的稳态信号将有助于神经系统疾病的原因或进展。然而，稳态信号和疾病之间的明确联系将需要对潜在信号系统的详细细胞和分子理解。目前，稳态信号传导的分子基础在很大程度上仍然未知。在过去的十年里，我们已经建立了一个模型系统，用于快速识别和表征果蝇神经系统中参与稳态信号转导的基因。我们最近的成功之一是证明了人类精神分裂症相关基因dysbindin对稳态信号传导至关重要。在初步的数据中，我们确定了两个新的蛋白质，控制突触前神经末梢内的稳态信号，包括一个新的蛋白激酶和蛋白磷酸酶。我们建议这些新的基因的特点，并定义它们如何在稳态信号的功能。这两个基因在人类中高度保守。

DESCRIPTION (provided by applicant): There is increasing evidence that neural function is stabilized by homeostatic signaling systems in organisms ranging from Drosophila to mouse and human. In each example, homeostatic signaling systems were identified following an experimental perturbation of neuronal or muscle excitability. In each experiment, the cells responded to the experimental perturbation by modulating ion channel abundance or synaptic transmission to counteract the perturbation and re-establish normal activity levels. It is now widely hypothesized that defective homeostatic signaling will contribute to the cause or progression of neurological disease. However, clear links between homeostatic signaling and disease will require a detailed cellular and molecular understanding of the underlying signaling systems. Currently, the molecular basis of homeostatic signaling remains largely unknown. Over the past ten years, we have established a model system for the rapid identification and characterization of genes involved in homeostatic signaling in the nervous system of Drosophila melanogaster. Among our recent successes has been the demonstration that a schizophrenia associated gene in human, dysbindin, is critical for homeostatic signaling. In preliminary data we identified two novel proteins that control homeostatic signaling within the presynaptic nerve terminal including a novel protein kinase and protein phosphatase. We propose to characterize these new genes and define how they function during homeostatic signaling. Both genes are highly conserved in human.