The role of the RIM-binding protein active zone scaffold in regulating neurotransmitter release at diverse central synapses (A05)

介导突触囊泡胞吐的蛋白支架如何促进大脑突触功能的广泛多样性，在很大程度上是未知的。我们将研究rim结合蛋白在确定两个已知功能差异的小鼠中枢突触的分子结构和功能中的作用。我们将利用生物化学、体内诱变和显微镜来表征RIM-BP2相互作用物及其功能含义。我们将研究替代突触特异性支架形成的假定机制，如RIM-BP2及其相互作用伙伴的异构体表达的变化，或蛋白质水平的变化。提出的实验有望揭示有助于活性区的功能结构的脚手架原理，并开辟了对突触编码多样性的生物学的新理解。

How the protein scaffolds that mediates synaptic vesicle exocytosis contributes to the brain wide diversity of synaptic function is largely unknown. We will examine the role of RIM-binding protein in defining the molecular architecture and function in two central murine synapses with known differences in function. We will characterize the RIM-BP2 interactors and their functional implication using biochemistry, in vivo mutagenesis and microscopy. We will examine putative mechanisms for alternative synapse specific scaffold formations such as variations in expression of isoforms of RIM-BP2 and it’s interaction partners, or variation of protein levels. The proposed experiments promise to reveal scaffolding principles that contribute to the functional architecture of the active zone and open up novel understanding of the biology that underlies diversity of synaptic coding.