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

该建议是基于PAR-6/aPKC复合物调节树突棘的发现 形态发生，它通过一种新的信号通路，涉及pi 90 RhoGAP和RhoA 好的该项目指导阶段的研究显示小GTPase Rnd 1是候选者 p190 RhoGAP和RhoA是PAR-6/aPKC介导p190 RhoGAP和RhoA作用的蛋白。本提案的目标1寻求 阐明PAR-6/aPKC复合物调节Rndl的分子机制。具体而言是 PAR复合物对Rndl表达和磷酸化的影响，以及Rnd/190相互作用将被研究。 考察为了进一步研究PAR复合体在突触功能中的作用，我们将阐明 PAR复合物调节多巴胺能突触传递的机制，并确定 PAR复合物的上游调节剂。最后，我们正在产生PAR-6C条件性敲除小鼠， 检验PAR复合物参与体内突触可塑性和记忆形成的假设。我 长期目标是了解调控树突棘形态发生的复杂信号机制 和突触可塑性，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.