MACROMOLECULAR ARCHITECTURE OF THE SYNAPSE

这个新项目分析了哺乳动物大脑突触的分子结构，最初的重点是突触后密度（PSD）。PSD的许多分子成分是已知的，但PSD是如此之大大约100亿Da，必须开发方法来了解其众多的分子成分是如何组织的。一种新的方法是将psd附着在玻璃上，用免疫金标记它们，然后冷冻并复制它们用于电子显微镜。迄今为止的工作揭示了形成PSD核心的晶格状结构，并为PSD-95贴上了沉重的标签。我们目前的研究重点是CaMKII酶，它是前脑psd的主要蛋白质。在压力下，CaMKII在细胞体和棘中形成聚集体，聚集在PSD的细胞质表面，这在很大程度上解释了压力下发生的增厚。我们已经提出，这种聚集能力允许它继续缓冲钙调蛋白，同时保护神经元免受过度磷酸化。我们目前正在研究CaMKII聚集的机制以及它在正常神经元功能中的作用。随着功能组分分布的确定，我们计划开发PSD-突触的大分子结构，PSD，突触结构，PSD-95, NR-1, CaMKII，结构生物学

This new project analyzes the molecular architecture of synapses in the mammalian brain with an initial focus on the postsynaptic density (PSD). Many molecular components of the PSD are known, but the PSD is so large approximately 10 billion Dathat methods had to be developed to understand how its numerous molecular components are organized. A new approach begins by attaching PSDs to glass, labeling them with immunogold, and then freezing and replicating them for electron microscopy. Work to date reveals a lattice-like structure that forms the core of the PSD and labels heavily for PSD-95. Our current focus is on the enzyme CaMKII which is the major protein in forebrain PSDs. During stress, CaMKII forms aggregates in cell bodies and in spines collects on the cytoplasmic surface of the PSD, accounting for much of the thickening that occurs during stress. We have proposed that this ability to aggregate allows it to continue to buffer calmodulin while protecting the neuron from excessive phosphorylation. We are currently investigating the mechanism of CaMKII aggregation as well as what role it may have in normal neuronal function. As the distributions of functional components are determined we plan to develop a macromolecular architecture of the PSD - synapse, PSD, synaptic structure, PSD-95, NR-1, CaMKII, structural biology