Cell cell adhesion among embryonic cells

描述（由申请人提供）：自从我们发现神经细胞 粘附分子，N-CAM，20多年前，已经很清楚， 细胞粘附分子（CAM）不仅介导细胞间的相互作用， 还诱导影响胚胎发育和成年生理的信号。在 这些拟议的研究，我们专注于N-CAM在调节关键的作用， 神经系统中的细胞功能我们的首要目标是 阐明了细胞膜上和细胞膜下的事件，通过这些事件，N-CAM结合到 细胞表面诱导细胞内信号。N-CAM诱导 转录因子NF-κ B作为范例，但研究将 扩展到其他N-CAM介导的事件。重组蛋白对应于 N-CAM的各种细胞外部分将用于检查结合事件， 和N-CAM胞质区的定点诱变将用于 分析细胞内事件。在第二个目的中，N-CAM诱导细胞凋亡的能力是通过诱导细胞凋亡来实现的。 神经干细胞分化为神经元， 异嗜性（非N-CAM）受体将在机制方面进行检查 刺激，受体参与，以及神经元的类型诱导 N-CAM结合。多价重组蛋白将用于诱导 反应，并与来自我们的N-CAM敲除小鼠的细胞联合应用 分离异嗜性受体在第三个目标中，我们将研究 N-CAM在诱导突触长时程增强（LTP）中的作用， 潜在的记忆和学习对于这些研究，突触动力学和 将在两种N-CAM敲除小鼠品系中比较形态学，一种具有 海马LTP和一个没有LTP。我们开发的一种新方法 将使用识别活动突触的群体。规定的机制的 这些研究所取得的成果应作为其他协调行动机制活动的范例。 他们还应该对CAM如何调节基因表达产生新的见解， 为神经干细胞的分化提供了新的试剂， 临床应用，并扩大我们的基本机制， 是记忆和学习的基础

DESCRIPTION (provided by applicant): Since our discovery of the neural cell adhesion molecule, N-CAM, over 20 years ago, it has become clear that binding by cell adhesion molecules (CAMs) not only mediates cell-cell interactions, but also induces signals that affect embryonic development and adult physiology. In these proposed studies, we focus on the role of N-CAM in regulating critical cellular functions in the nervous system. Our first aim is designed to elucidate the events at and under the cell membrane by which N-CAM binding to the cell surface induces intracellular signals. The ability of N-CAM to induce the transcription factor NF-KB serves as the paradigm, but the studies will be extended to other N-CAM-mediated events. Recombinant proteins corresponding to various extracellular portions of N-CAM will be used to examine binding events, and site-directed mutagenesis of the N-CAM cytoplasmic region will be used to analyze intracellular events. In the second aim, the ability of N-CAM to induce the differentiation of neural stem cells into neurons by binding to heterophilic (non-N-CAM) receptors will be examined in terms of the mechanism of stimulation, the receptors involved, and the types of neurons induced by N-CAM binding. Multivalent recombinant proteins will be used to induce the response and be applied in conjunction with cells from our N-CAM knock-out mice to isolate heterophilic receptors. In the third aim, we will examine the role of N-CAM in inducing long term potentiation (LTP) of synapses, a key process underlying memory and learning. For these studies, synaptic dynamics and morphology will be compared in two strains of N-CAM knock-out mice, one with hippocampal LTP and one without LTP. A new method we have developed for identifying populations of active synapses will be used. The mechanisms defined by these studies should serve as exemplars for the activities of other CAMs. They should also yield new insights into how CAMs regulate gene expression, provide novel reagents for differentiating neural stem cells for potential clinical use, and expand our knowledge of the fundamental mechanisms that underlie memory and learning.