Elucidating the function of the Lipid-Binding Protein OBI-1 in Pristionchus pacif

阐明太平洋Pristionchus pacif中脂质结合蛋白OBI-1的功能

• 批准号: 8871734
• 负责人: Ray L Hong
• 金额: $ 10.88万
• 依托单位: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8871734
• 关键词: Acetates; Alleles; Animal Model; Animals; Bacteria; Behavior; Binding; Binding Proteins; Brugia malayi; Caenorhabditis elegans; Cells; Cholesterol Esters; Communication; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Development; Developmental Process; Disease; Drosophila genus; Environment; Epithelial Cells; Evolution; Excretory function; Exhibits; Filarial Elephantiases; Funding; Genes; Health; Histocompatibility Testing; Hour; Human; Insect Vectors; Insecta; Intercept; Invertebrates; Investigation; Knowledge; Life; Ligands; Lipid Binding; Livestock; Mammals; Mediating; Membrane; Modeling; Molecular; Molecular Chaperones; Molecular Genetics; Names; Nematoda; Neuroglia; Neurons; Nomenclature; Nuclear; Odors; Order Coleoptera; Organ; Orthologous Gene; Parasitic nematode; Pathway interactions; Phenotype; Pheromone; Physiology; Population; Proteins; Recombinants; Sampling; Sensory; Signal Pathway; Signal Transduction; Smell Perception; Supporting Cell; System; Testing; Tissues; Transcript; Translating; United States National Institutes of Health; Up-Regulation; Variant; Work; bactericidal permeability increasing protein; base; cell type; comparative; extracellular; gain of function; genetic approach; improved; lipopolysaccharide-binding protein; mutant; neuron development; neurophysiology; promoter; public health relevance; receptor; receptor binding; reconstitution; response; transcriptome sequencing

DESCRIPTION (provided by applicant): Pristionchus species are nematodes that associate with specific beetles and represent a poorly understood but highly prevalent type of nematode-insect interaction known as necromeny. The working model for how Pristionchus nematodes maintain specific insect interactions is by intercepting the intra-species communications of their host insects. Given the multitude of nematode associations with insect and mammalian hosts, the beetle-associated Pristionchus pacificus represents a much needed knowledge bridge between the free-living model organism Caenorhabditis elegans and human filarial nematodes such as Brugia malayi and Wucheria bancrofti. This is especially relevant to human health since filarial nematodes also require insect vectors to transmit diseases such as lymphatic filariasis. Knowledge of the molecular physiology of insect pheromone attraction will have a direct impact on our understanding of olfaction in nematodes, which can ultimately translate into improving treatments against parasitic nematodes that afflict an estimated 1.3 billion people worldwide (WHO). Our recent NIH-funded study revealed that a lipid binding protein, OBI-1, mediates host insect pheromone sensing through the cGMP signaling pathway that is found in many sensory cells of animals. OBI-1 belongs to a class of highly conserved but functionally diverse secreted lipid-binding proteins, including lipopolysaccharide-binding proteins (LBPs), bactericidal permeability-increasing proteins (BPIs), and cholesteryl ester transfer proteins in mammals. We hypothesize that the expression of OBI-1 in the glial cells that support chemosensory neurons is required for the nematode's olfactory organ to recognize the beetle pheromone. We speculate that OBI-1 may act as an extracellular receptor chaperone to guide pheromone molecules to membrane-bound receptors, or as a signal terminator to remove the pheromone from membrane bound receptors. Our primary aims are to determine if OBI-1 mediates olfaction through the glial cells and if there is direct interaction between OBI-1 and the pheromone molecule. Our long-term focus is to interrogate how OBI-1 genetically interacts with other factors the cGMP pathway during odor sensing, such as the cGMP-dependent protein kinase (PKG) EGL-4.

描述(申请人提供)：Pristionchus物种是与特定甲虫相关的线虫，代表一种鲜为人知但非常普遍的线虫-昆虫相互作用类型，称为死亡。Pristionchus线虫维持特定昆虫相互作用的工作模式是通过拦截它们的宿主昆虫的种内通信。由于线虫与昆虫和哺乳动物宿主之间存在着大量的联系，与甲虫相关的太平洋拟线虫代表了自由生活的模式生物秀丽线虫和人类丝虫(如马来丝虫和班氏吴氏线虫)之间亟需的知识桥梁。这与人类健康特别相关，因为丝虫线虫也需要昆虫媒介来传播疾病，如淋巴丝虫病。对昆虫信息素吸引的分子生理学的了解将直接影响我们对线虫嗅觉的理解，这最终可以转化为改进对寄生线虫的治疗，据估计，全世界有13亿人(世卫组织)。我们最近由美国国立卫生研究院资助的研究发现，一种脂结合蛋白OBI-1通过cGMP信号通路介导宿主昆虫信息素的感知，该信号通路存在于动物的许多感觉细胞中。OBI-1是一类高度保守但功能多样的分泌脂结合蛋白，包括哺乳动物中的脂多糖结合蛋白(LBPS)、杀菌通透性增加蛋白(BPI)和胆固醇酯转移蛋白。我们假设，OBI-1在支持化学感觉神经元的胶质细胞中的表达是线虫的嗅觉器官识别甲虫信息素所必需的。我们推测，OBI-1可能作为细胞外受体伴侣，引导信息素分子与膜结合受体结合，或作为信号终止剂，将信息素从膜结合受体中移除。我们的主要目标是确定OBI-1是否通过神经胶质细胞介导嗅觉，以及OBI-1与信息素分子之间是否存在直接相互作用。我们的长期重点是询问OBI-1如何在基因上与气味感知过程中cGMP途径的其他因素相互作用，例如cGMP依赖的蛋白激酶(PKG)EGL-4。