Molecular mechanisms and synaptic functions of kainate receptor SUMOylation

红藻氨酸受体SUMO化的分子机制和突触功能

基本信息

批准号：
BB/F00723X/1
负责人：
Jeremy Henley
金额：
$ 120.71万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF00723X%2F1
关键词：
Molecular mechanisms synaptic functions kainate

项目摘要

Efficient communication between neurones at synapses is required for proper brain function. This communication uses chemical transmitters and relies on the presence of receptor proteins at the synapse surface. A key feature of this system is that the number of receptors changes depending on the activity at the synapse. We have found that for one type of receptor called the kainate receptor, binding of the transmitter leads to attachment of a small protein called SUMO and this results in the receptor being removed from the surface into the cell (where it can no longer function) by a mechanism called endocytosis. Preventing SUMO attachment to kainate receptors blocks endocytosis. We go on to demonstrate that this process regulates communication between neurones. This is significant because kainate receptors regulate the general excitability of neurones and synaptic transmission and their dysfunction has been implicated in diseases such as epilepsy and Huntington's disease. In addition, we show that in addition to the receptor we have characterised, there are many other proteins present at synapses that undergo similar addition of SUMO. The aim of this proposal is to go on to work out some of the details of how this process works. Specifically we want to find out what change in the receptor allows it to bind SUMO and what molecular changes take place once the receptor is SUMOylated. We believe these experiments will have very important implications for understanding how synapses function. Furthermore, once we shed light on how kainate receptors are handled in normal cells we can then gain insight into what happens in injured or diseased cells and try to formulate strategies to compensate for or repair the problems.

正常的大脑功能需要神经元之间的有效沟通。该通信使用化学发射器，并依赖于突触表面的受体蛋白的存在。该系统的一个关键特征是受体数量根据突触的活动而变化。我们发现，对于一种称为Kainate受体的受体类型，发射器的结合会导致一种称为Sumo的小蛋白质的附着，这会导致受体从表面移入细胞中（不再能够通过一种称为内吞作用的机制）将受体移至细胞中。防止emo依附在海藻酸盐受体上，阻断内吞作用。我们继续证明这一过程调节神经元之间的沟通。这很重要，因为海谷酸盐受体调节神经元和突触传播的一般兴奋性及其功能障碍与癫痫和亨廷顿氏病等疾病有关。此外，我们表明，除了我们表征的受体外，在突触中还有许多其他蛋白质会经历相似的相扑。该提案的目的是继续阐明该过程如何工作的一些细节。具体而言，我们想找出受体中的变化允许它结合相扑，一旦受体被汇总，就会发生哪些分子变化。我们认为，这些实验将对理解突触如何运作具有非常重要的意义。此外，一旦我们阐明了如何在正常细胞中处理海藻酸盐受体，我们就可以深入了解受伤或患病细胞中发生的情况，并尝试制定策略以补偿或修复问题。