Synaptic Function in the Nematode C. Elegans

线虫的突触功能 线虫

• 批准号: 8269720
• 负责人: ERIK M JORGENSEN
• 金额: $ 32.26万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8269720
• 关键词: Acceleration; Action Potentials; Adaptor Protein Complex alpha Subunits; Alleles; Alzheimer' s Disease; Animals; Ataxia; Binding; Biochemical; Biogenesis; Biological; Biological Assay; C2 Domain; Caenorhabditis elegans; Calcium; Cells; Clathrin; Clathrin Adaptors; Clathrin-Coated Vesicles; Cleaved cell; Communication; Complex; Data; Defect; Disease; Dynamin; Electron Microscopy; Endocytosis; Endocytosis Pathway; Exocytosis; Fatigue; Fluorescence; Frequencies; Future; Genetic; Health; Huntington Disease; Knock-in Mouse; Label; Lead; Measures; Mediating; Membrane; Mutation; Nematoda; Nervous system structure; Neurodegenerative Disorders; Neuroglia; Neurons; Parkinson Disease; Pathway interactions; Pharmacotherapy; Phospholipid Interaction; Phospholipids; Physiology; Play; Process; Proteins; Recovery; Recruitment Activity; Recycling; Research; Research Personnel; Resolution; Role; Signal Transduction; Structure; Synapses; Synaptic Transmission; Synaptic Vesicles; Syndrome; Techniques; Temperature; Testing; Transcription Factor AP-2 Alpha; Vesicle; Yeasts; coated pit; innovation; mutant; nervous system disorder; neurotransmission; neurotransmitter release; novel; null mutation; receptor; receptor mediated endocytosis; response; sensor; synaptic function; synaptogyrin; synaptojanin; synaptotagmin; vesicle-associated membrane protein; weapons

DESCRIPTION (provided by applicant): Communication between nerve cells takes place by the release of neurotransmitters at synapses. Signaling can be extremely rapid - transmitting information via hundreds of action potentials per second. It is not possible to synthesize new synaptic vesicles at this pace, so rapid recycling is essential. Although endocytosis at the synapse is at the core of synaptic transmission, the exact mechanism of this process has continued for over 35 years without resolution. Aim 1. In non-neuronal cells, clathrin is the central player in endocytosis. We will test the role of clathrin in synaptic recycling. Aim 2. Adaptins are thought to collect cargo molecules for recycling and connect them to the clathrin coat. We will test the role of these complexes in localizing specific synaptic cargoes and in promoting endocytosis. Aim 3. Synaptotagmin is not only the main calcium sensor in exocytosis, but also a central player in endocytosis at the synapse. We will examine the role of synaptotagmin in recruiting cargo and adapters into the endocytosis pathway. Aim 4. Dynamin is thought to be required for pinching off endocytosing vesicles. However, dynamin is not required in yeast cells, and recent data indicate that dynamin might only be essential during high frequency stimulation at the synapse. We will examine the role of dynamin in synaptic recycling using null and temperature-sensitive dynamin mutations. There is growing evidence that understanding endocytosis will have direct impact on applied health research, since defects in endocytosis may play causative roles in many neuronal diseases, including Huntington's Disease, the ataxias, Parkinson's Disease, Hermansky-Pudlack syndrome, and Alzheimer's Disease. It is our hope that understanding the process of endocytosis may lead to drug therapies for these diseases in the future. Finally, in the course of resolving this biological question, we are developing innovative new techniques that will aid many other researchers to bring new scientific weapons to these and other problems. PUBLIC HEALTH RELEVANCE: Nerve cells communicate via synaptic transmission, but defects in this process can lead to diseases of the nervous system, such as Parkinson's Disease and Alzheimer's Disease. By studying the basic processes of neurotransmission, we hope to understand the causes of neurodegenerative diseases as well as develop novel therapies.

描述(申请人提供)：神经细胞之间的交流是通过在突触释放神经递质来进行的。信号可以通过每秒数百个动作电位极其迅速地传递信息。以这种速度合成新的突触囊泡是不可能的，所以快速回收是必不可少的。虽然突触的内吞作用是突触传递的核心，但这一过程的确切机制已经持续了35年以上，但仍未得到解决。目的：1.在非神经细胞中，网状蛋白是胞吞作用的核心分子。我们将测试网状蛋白在突触再循环中的作用。目标2.Adaptins被认为可以收集货物分子进行回收，并将它们连接到网状蛋白涂层上。我们将测试这些复合体在定位特定突触货物和促进内吞方面的作用。目的3.突触凝集素不仅是胞吐作用中的主要钙感受器，也是突触内吞作用的核心分子。我们将研究突触素在招募货物和适配器进入内吞途径中的作用。目的4.动力素被认为是掐走内吞小泡所必需的。然而，酵母细胞并不需要动力蛋白，最近的数据表明，动力蛋白可能只在突触受到高频刺激时才是必需的。我们将使用零和温度敏感的Dynamin突变来研究Dynamin在突触再循环中的作用。越来越多的证据表明，了解内吞作用将对应用的健康研究产生直接影响，因为内吞作用缺陷可能在许多神经元疾病中起致病作用，包括亨廷顿病、共济失调、帕金森病、赫曼斯基-布德拉克综合征和阿尔茨海默病。我们希望，了解内吞作用的过程可能会导致未来对这些疾病的药物治疗。最后，在解决这个生物学问题的过程中，我们正在开发创新的新技术，这些技术将帮助许多其他研究人员为这些和其他问题带来新的科学武器。 与公共健康相关：神经细胞通过突触传递进行交流，但这一过程中的缺陷可能会导致神经系统疾病，如帕金森氏症和阿尔茨海默氏症。通过研究神经传递的基本过程，我们希望了解神经退行性疾病的原因以及开发新的治疗方法。