Synaptic Function in the Nematode C. Elegans

描述（由申请人提供）：神经细胞之间的交流是通过突触释放神经递质进行的。信号可以非常迅速地通过每秒数百个动作电位传递信息。以这种速度合成新的突触囊泡是不可能的，因此快速循环是必不可少的。虽然突触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超过35年，没有得到解决。目的1。在非神经元细胞中，网格蛋白是内吞作用的核心参与者。我们将测试网格蛋白在突触循环中的作用。目标2。适应性被认为是收集货物分子进行回收，并将它们连接到网格蛋白外壳上。我们将测试这些复合物在定位特定突触货物和促进内吞作用中的作用。目标3。突触塔蛋白不仅是胞外分泌的主要钙传感器，也是突触内吞作用的核心参与者。我们将研究synaptotagmin在招募货物和转接头进入内吞途径中的作用。目标4。动力蛋白被认为是拧断内吞囊泡所必需的。然而，动力蛋白在酵母细胞中是不需要的，最近的数据表明动力蛋白可能只在突触的高频刺激中是必需的。我们将使用零和温度敏感的动力蛋白突变来研究动力蛋白在突触循环中的作用。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、Hermansky-Pudlack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，这将帮助许多其他研究人员为这些问题和其他问题带来新的科学武器。

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.