Molecular regulation of nicotinic acetylcholine receptors

烟碱乙酰胆碱受体的分子调节

基本信息

批准号：
9029173
负责人：
Alison Philbrook
金额：
$ 3.03万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-02 至 2018-02-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9029173
关键词：
Address Affect Alzheimer&apos s Disease Animals Binding Biological Biological Models Biology Brain Caenorhabditis elegans Cell surface Cells Cessation of life Cholinergic Receptors Complement Complex Dendrites Development Disease Drug Addiction Electrophysiology (science)Foundations Future Genetic Immunoglobulin Domain Immunoglobulins Life Link Maintenance Mediating Microscopy Molecular Motor Neurons Nervous system structure Neurobiology Neurons Nicotine Nicotine Dependence Nicotinic Receptors Pattern Phenotype Population Process Property Protein Family Proteins Public Health Receptor Activation Regulation Resolution Role Shapes Signal Transduction Site Smoking Specificity System Techniques Testing Tobacco Tobacco smoking Training United States Up-Regulation Work Xenopus oocyte addiction career cholinergic disorder prevention genetic approach genetic manipulation in vivo inhibitory neuron member mutant nerve supply nervous system disorder novel overexpression postsynaptic premature presynaptic public health relevance receptor receptor expression receptor function reconstitution research study smoking cessation therapy development tool trafficking

项目摘要

DESCRIPTION (provided by applicant): Smoking-related diseases result in more than 400,000 premature deaths in the United States each year1, yet thousands struggle with smoking cessation. Nicotine, the major addictive component in tobacco, interacts with specific classes of nicotinic acetylcholine receptors (nAChRs), altering the functional state of the receptors and expression at the cell surface. Although the role of nAChRs in nicotine addiction has been well established, mechanisms for the biological regulation of these receptors during normal brain function and following nicotine exposure are poorly defined. In this proposal, I will use the model system C. elegans to investigate the dynamics of nAChRs on the neuronal cell surface. [In Aim 1, I will define the subunit composition of nAChRs expressed on the dendrites of GABAergic motor neurons. Secondly, I will investigate the role of OIG-1, an immunoglobulin domain protein, in nicotinic receptor clustering.] Finally, in the third Aim I will investigate how neuronal activity and nicotine exposure shape the dynamics and subcellular distribution of nAChRs. These studies will address fundamental questions about the biology of nAChRs and provide me with strong training in genetics, microscopy, and electrophysiology techniques that will be essential tools in my continuing scientific development.

描述（由适用提供）：与吸烟有关的疾病每年在美国造成40万多人死亡，但成千上万的人因戒烟而挣扎。尼古丁是烟草中的主要附加成分，它与特定类别的烟碱乙酰胆碱受体（NACHR）相互作用，改变了受体的功能状态和细胞表面的表达。尽管NACHR在尼古丁成瘾中的作用已经建立了很好的确定，但在正常脑功能和尼古丁暴露后，这些受体的生物学调节机制的定义很差。在此提案中，我将使用模型系统C.秀丽隐杆线虫研究神经元细胞表面上NACHR的动力学。 [在AIM 1中，我将定义在GABA能运动神经元树突上表达的NACHR的亚基组成。其次，我将研究OIG-1（一种免疫球蛋白结构蛋白）在烟碱受体聚类中的作用。]最后，在第三个目标中，我将研究如何研究神经元活性和尼古丁暴露塑造了NACHR的动力学和亚细胞分布。这些研究将解决有关NACHRS生物学的基本问题，并为我提供有关遗传学，显微镜和电生理技术的强有力培训，这些技术将是我持续的科学发展中必不可少的工具。