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Regulation of post-synaptic receptor recycling by synaptotagmin 3

突触结合蛋白 3 对突触后受体回收的调节

基本信息

批准号：
210536680
负责人：
Dr. Camin Dean
金额：
--
依托单位：
Standort Berlin
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/210536680?language=en
关键词：
Regulation post synaptic receptor recycling

项目摘要

In the last funding period we proposed to investigate the localization of different synaptotagmin (syt) isoforms to distinct vesicle subtypes in neurons, using a new technique to isolate vesicles from very small amounts of neuronal tissue, developed by a postdoc in the lab (now published: Ahmed et al. Nat. Protocols 2013). Data from the last funding period (now published: Dean et al. Mol. Biol. Cell 2012) suggested that members of the syt family of molecules are differentially localized to distinct vesicle subtypes in neurons. In a further characterization of one isoform, syt4, we found that syt4/ BDNF-harboring vesicles with distinct fusion properties are sorted to axons versus dendrites (now published: Dean et al., J. Neurosci. 2012). While examining the properties of the syt isoforms, we discovered, in preliminary data described below, that syt3 is uniquely localized exclusively to the post-synaptic membrane, where it regulates endocytosis of post-synaptic AMPA receptors. This is a particularly interesting finding because post-synaptic receptor recycling to and from the post-synaptic membrane is essential for long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength - a fundamental property of neurons that is crucial for learning and information storage in the brain. But the molecular machinery mediating the exo- and endocytosis of receptors to and from the post-synaptic membrane is poorly understood. We propose to determine, using a combination of imaging, biochemical, and electrophysiological approaches, if syt3 is the post-synaptic calcium sensor that regulates recycling of receptors during synaptic plasticity. This will not only reveal the location and function of this unique syt isoform in neurons, but will also answer a long-standing question regarding how post-synaptic receptor recycling is regulated to affect synaptic plasticity.

在上一个资助期间，我们提出研究不同的突触结合蛋白（syt）亚型在神经元中的不同囊泡亚型的定位，使用一种新技术从非常少量的神经元组织中分离囊泡，该技术由实验室的博士后开发（现已发表：Ahmed et al. Nat. Protocols 2013）。上一个资助期的数据（现已出版：Dean et al. Mol. Cell 2012）表明，syt分子家族的成员差异性地定位于神经元中不同的囊泡亚型。在一种同种型syt 4的进一步表征中，我们发现具有不同融合特性的携带syt 4/BDNF的囊泡被分选为轴突与树突（现在发表：Dean等人，神经科学杂志2012年）。在检查syt同种型的性质时，我们发现，在下面描述的初步数据中，syt 3唯一地仅定位于突触后膜，在那里它调节突触后AMPA受体的内吞作用。这是一个特别有趣的发现，因为突触后受体在突触后膜上的再循环对于突触强度的长时程增强（LTP）和长时程抑制（LTD）至关重要--这是神经元的基本特性，对于学习至关重要大脑中的信息存储。但是介导受体进出突触后膜的胞吞和胞吞的分子机制却知之甚少。我们建议确定，使用成像，生物化学和电生理方法的组合，如果syt 3是突触后钙传感器，调节受体在突触可塑性的回收。这不仅将揭示这种独特的syt亚型在神经元中的位置和功能，而且还将回答一个长期存在的问题，即突触后受体的再循环是如何调节的，从而影响突触可塑性。