KIN-29 SIK SIGNALING THE THEREGULATION OF FOOD-RELATED BEHAVIORS & DEVELOPMENT

KIN-29 SIK 发出食品相关行为监管信号

• 批准号: 8168235
• 负责人: ALEXANDER VAN DER LINDEN
• 金额: $ 17.82万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168235
• 关键词: Afferent Neurons; Animals; Behavior; Body Size; Caenorhabditis elegans; Chemoreceptors; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupled; Development; Environment; Event; Family member; Feeding behaviors; Food; Funding; Gene Expression; Genes; Genetic Screening; Grant; Habits; Homeostasis; Homologous Gene; Institution; Mammals; Metabolism; Molecular Profiling; Neurons; Nutritional status; Phosphorylation; Phosphotransferases; Physiology; Research; Research Personnel; Resources; Signal Pathway; Signal Transduction; Source; Time; Transcriptional Regulation; United States National Institutes of Health; animal behavior development; feeding; fly; food quality; mRNA tagging; mature animal; mutant; neuron component; next generation; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The availability and quality of food fluctuates over time in an animal's environment. When food is scarce, an animal must undergo changes in its behavior, metabolism and physiology to promote survival. An animal must also regulate its feeding habits depending on nutritional status in order to maintain physiological homeostasis. Salt-inducing kinases (SIKs) are important regulators of energy homeostasis, and feeding/fasting responses in mammals. We previously found that KIN-29, the C. elegans homolog of SIK, modulates chemoreceptor (CR) gene expression, feeding behaviors and body size. We believe that CR gene modulation underlies, at least in part, the ability of animals to correctly transduce food-derived signals to modulate feeding and body-size. To further dissect the KIN-29 signaling pathways by which food signals are integrated to modulate behavior and development, we are taking three parallel strategies to define new targets of KIN-29. In the first, we are determining the gene expression profiles of specific sensory neurons using next-generation sequencing coupled to a mRNA-tagging approach. Preliminary results using microarrays indicate that a large subset of genes predicted to function in transcriptional regulation and phosphorylation events are up- and down-regulated, respectively, in wild-type and kin-29 mutants in chemosensory neurons. Secondly, we are examining a KIN-29-dependent CR gene whose expression in the ADL chemosensory neurons is acutely altered by the presence and absence of food in adult animals. We will take advantage of these observations to identify the components and neurons by which food signals alter CR gene expression using genetic screens. Finally, we are examining the function the single C. elegans homolog of CRTC/TORC, which is phosphorylated by SIK family members and is an important regulator of metabolism in mammals and flies. Together these experiments will provide a detailed understanding of the remarkably complex effects of food on animal development and behavior.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在动物的环境中，食物的可获得性和质量会随着时间的推移而波动。当食物匮乏时，动物必须经历其行为、新陈代谢和生理的变化才能促进生存。动物还必须根据营养状况调整其摄食习惯，以维持生理动态平衡。盐诱导蛋白激酶(SIKs)是哺乳动物能量动态平衡和摄食/禁食反应的重要调节因子。我们先前发现，线虫SIK的同源物KIN-29可以调节化学受体(CR)基因的表达、摄食行为和个体大小。我们认为，至少在一定程度上，CR基因调节是动物正确地传递食物来源的信号以调节摄食和体型的能力的基础。为了进一步剖析KIN-29信号通路，通过它整合食物信号来调节行为和发育，我们采取了三个平行的策略来定义KIN-29的新靶点。首先，我们正在使用下一代测序和信使核糖核酸标签相结合的方法来确定特定感觉神经元的基因表达谱。使用微阵列的初步结果表明，在化学感觉神经元的野生型和KIN-29突变体中，被预测具有转录调节和磷酸化事件功能的一大部分基因分别上调和下调。其次，我们正在研究一种依赖于KIN-29的CR基因，它在ADL化学感觉神经元中的表达会因成年动物的食物存在和缺乏而急剧改变。我们将利用这些观察结果来确定食物信号通过遗传筛选改变CR基因表达的成分和神经元。最后，我们正在研究CRTC/TORC的单个线虫同源物的功能，它由SIK家族成员磷酸化，是哺乳动物和苍蝇代谢的重要调节因子。总之，这些实验将详细了解食物对动物发育和行为的极其复杂的影响。