Signal integration at scaffolding proteins: Identification and functional analysis of A-Kinase-Anchoring Proteins in memory processing

学习和记忆需要不同分子信号通路之间的协同作用，这些分子信号通路共同在大脑内建立了一个整合的计算网络。虽然个别途径是众所周知的，它们的整合及其与学习和记忆的相关性的分子机制还没有。最近，我可以确定家庭的A-激酶锚定蛋白（AKAP）作为一个这样的分子整合器使用的果蝇嗅觉条件反射范例。在这个应用程序中，我将把这个新结果加起来，并将讨论以下主题：（1）哪些AKAP参与了不同动机记忆的加工和巩固？(2)哪些信号通路整合在特定的AKAP上，分子机制是什么？(3)在细胞水平上保持信号特异性的机制是什么？考虑到信号计算与大脑的整合性质，解决这些问题将有助于扩展当代体内记忆处理模型。

Learning and memory requires a concerted interaction between different molecular signaling pathways, which altogether build up an integrative computational network within the brain. Although the individual pathways are well known, the molecular mechanisms of their integration and its relevance for learning and memory are not. Recently, I could identify the family of A-kinase-anchoring-proteins (AKAPs) as one such molecular integrator by use of the well established Drosophila olfactory conditioning paradigm. In this application I should add up on this new result and will address following topics: (1) Which AKAPs are involved in processing and consolidation of differently motivated memories? (2) Which signaling pathways are integrated at the particular AKAPs and what is the molecular mechanism? (3) What is the mechanism that preserves signaling specificity on a cellular level? Answering these questions will help to extend contemporary models of in vivo memory processing by taking into account the integrative nature of signal computation with the brain.