The PAR-6/aPKC Polarity Complex in Synaptic Assembly and Function

这一建议是基于PAR-6/aPKC复合体调节树突棘的发现 形态发生，它通过一种新的信号通路实现这一点，涉及pi90 RhoGAP和RhoA GTP酶。在该项目指导阶段的研究表明，小GTP酶Rnd1是一个候选 介导PAR-6/aPKC对p190RhoGAP和RhoA影响的蛋白质。本提案的目标1旨在 目的：阐明PAR-6/aPKC复合体调控RNDL的分子机制。具体地说， PAR复合体对RND1表达和磷酸化的影响以及RND/190相互作用将是 检查过了。为了进一步研究PAR复合体在突触功能中的作用，我们将阐明 PAR复合体调节谷氨酸能突触传递的机制，并鉴定 PAR综合体的上游监管机构。最后，我们正在培育PAR-6C条件性基因敲除小鼠 验证PAR复合体参与体内突触可塑性和记忆形成的假设。我的 长期目标是了解调控树突棘形态发生的复杂信号机制 以及突触的可塑性，以及它们如何在体内转化为记忆的形成和维持。

The proposal is based on the finding that the PAR-6/aPKC complex regulates dendritic spine morphogenesis, and it does so through a novel signaling pathway involving pi90 RhoGAP and the RhoA GTPase. Studies during the mentored phase of this project revealed the small GTPase Rnd1 as a candidate protein for mediating the effects of PAR-6/aPKC on p190RhoGAP and RhoA. Aim 1 of this proposal seeks to elucidate the molecular mechanism by which the PAR-6/aPKC complex regulates Rndl. Specifically, the effect of the PAR complex on Rndl expression and phosphorylation, and Rnd/190 interaction will be examined. To further examine the role of the PAR complex in synaptic function, we will elucidate the mechanisms by which the PAR complex regulates glutamatergic synaptic transmissioin, and identify the upstream regulators of the PAR complex. Finally, we are generating PAR-6C conditional knockout mice to test the hypothesis that the PAR complex is involved in synaptic plasticity and memory formation in vivo. My long term goal is to understand the complex signaling mechanisms regulating dendritic spine morphogenesis and synaptic plasticity, and how they translate to memory formation and maintenance in vivo.