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：
8835674
负责人：
Alison Philbrook
金额：
$ 2.98万
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/8835674
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 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（由申请人提供）：在美国，与吸烟相关的疾病每年导致超过 400,000 人过早死亡1，但仍有数千人因戒烟而苦苦挣扎，尼古丁是烟草中的主要成瘾成分，与特定类别的烟碱乙酰胆碱受体相互作用。 nAChRs），改变受体的功能状态和细胞表面的表达，尽管 nAChRs 在尼古丁成瘾中的作用已经存在。虽然已经明确，但在正常大脑功能和尼古丁暴露后这些受体的生物调节机制尚不清楚。在本提案中，我将使用线虫模型系统来研究神经细胞表面 nAChR 的动态。 [在目标 1 中，我将定义 GABA 能运动神经元树突上表达的 nAChR 的亚基组成，其次，我将研究免疫球蛋白结构域蛋白 OIG-1 在细胞中的作用。烟碱受体聚类。]最后，在第三个目标中，我将研究如何神经元活动和尼古丁暴露塑造了 nAChR 的动态和亚细胞分布。这些研究将解决有关 nAChR 生物学的基本问题，并为我提供遗传学、显微镜学和电生理学技术方面的强有力的培训，这些技术将成为我持续科学发展的重要工具。