Mechanisms of pheromone signal transduction in C. elegans

线虫信息素信号转导机制

• 批准号: 8062957
• 负责人: Danna Mindy Zeiger
• 金额: $ 2.32万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8062957
• 关键词: Ablation; Adult; Affect; Animal Model; Animals; Behavior; Behavior Disorders; Behavioral; Biological Models; Brain; Caenorhabditis elegans; Chemicals; Cues; Data; Development; Disease; Esthesia; Functional disorder; Genes; Genome; Goals; Hormonal; Hormones; Human; Lead; Mammals; Mediating; Mutation; Neurons; Neurosecretory Systems; Obesity; Odors; Organism; Partner in relationship; Pathway interactions; Pheromone; Pheromone Receptors; Physiology; Process; Protein Tyrosine Phosphatase; Role; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Site; Smell Perception; Staging; System; Testing; Work; genetic analysis; hormone regulation; insight; intercellular communication; mutant; neurotransmission; public health relevance; receptor; research study; response; transmission process

DESCRIPTION (provided by applicant): Pheromones act as both short-term olfactory cues that signal danger or the presence of mates, as well as long-term cues, which mediate changes in development and physiology via modulation of the neuroendocrine axis. Little is known about the mechanisms by which pheromone signals are transduced to modulate neurohormonal signaling in mammals, although dysregulation of this signaling can result in developmental and behavioral disorders. Olfactory signal transduction mechanisms are highly conserved across organisms, as are mechanisms of neuronal transmission, indicating that studying these processes in model organisms may provide insights into related processes in higher organisms. In C. elegans, the dauer pheromone regulates entry into the alternate dauer developmental stage via regulation of hormonal signaling, and provides an excellent model system in which to explore how pheromone signals are recognized and transduced to govern a critical developmental decision. The recent identification of both the structurally related ascarosides comprising dauer pheromone in C. elegans, and the first two pheromone receptors in C. elegans, whose mutants are defective in pheromone-mediated regulation of hormonal signaling, remains elusive in other model organisms. The goal of this proposal is to identify additional receptors required for pheromone signal transduction, and to characterize a gene required for inter-neuronal pheromone signal transmission. This work will contribute to our understanding of the pathways by which pheromones regulate critical behavioral and developmental decisions, and how dysfunction of these pathways can lead to impaired development, behavioral disorders, and obesity. The proposed specific aims are: 1. Identification of the neurons and receptors required for C3 ascaroside signal transduction ascaroside. 2. Identification of intercellular pheromone signaling pathways. PUBLIC HEALTH RELEVANCE: Pheromones are secreted molecules that communicate immediate and long-term signals among animals of the same species. For a complete understanding of how humans smell, and how odors affect development and behavior, a thorough understanding of the mechanisms of detecting and relaying pheromonal signals is necessary. This work will lead to a better understanding of how the brain processes chemical signals, and how dysfunction of the chemosensory system leads to impaired development, behavioral disorders, and obesity.

描述(申请人提供)：信息素既可以作为短期嗅觉信号，发出危险或配偶存在的信号，也可以作为长期信号，通过调节神经内分泌轴来调节发育和生理变化。关于信息素信号如何被转导来调节哺乳动物的神经激素信号的机制，人们知之甚少，尽管这种信号的失调可能导致发育和行为障碍。嗅觉信号转导机制在生物体中高度保守，神经元传递机制也是如此，这表明在模式生物中研究这些过程可能会为深入了解高等生物体的相关过程提供帮助。在线虫中，Dauer信息素通过调节激素信号调节进入交替的Dauer发育阶段，并提供了一个很好的模型系统，在其中探索信息素信号是如何识别和传递的，以控制关键的发育决策。最近对线虫中含有Dauer信息素的结构相关的蛔虫苷和线虫中的前两个信息素受体的鉴定，在其他模式生物中仍然是未知的，因为线虫的突变体在信息素介导的激素信号调节方面存在缺陷。这项建议的目的是确定信息素信号转导所需的额外受体，并鉴定神经元间信息素信号传递所需的基因。这项工作将有助于我们理解信息素调节关键行为和发育决定的途径，以及这些途径的功能障碍如何导致发育障碍、行为障碍和肥胖。提出的具体目标是：1.鉴定C3蛔虫苷信号转导所需的神经元和受体。2.细胞间信息素信号通路的鉴定。 与公共健康相关：信息素是一种分泌分子，在同一物种的动物之间传递即时和长期的信号。为了完全了解人类的气味，以及气味如何影响发育和行为，彻底了解信息素信号的检测和传递机制是必要的。这项工作将有助于更好地理解大脑如何处理化学信号，以及化学感觉系统的功能障碍如何导致发育障碍、行为障碍和肥胖。