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: 8475301
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8475301
• 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; 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（由申请人提供）：Pristionchus种是与特定甲虫相关的线虫，代表了一种知之甚少但非常普遍的线虫-昆虫相互作用类型，称为坏死性。Pristionchus线虫如何维持特定的昆虫相互作用的工作模式是通过拦截其宿主昆虫的种内通信。鉴于线虫与昆虫和哺乳动物宿主的多种关系，甲虫相关的太平洋棱纹线虫代表了自由生活模式生物秀丽隐杆线虫和人类丝虫线虫（如马来丝虫和班氏丝虫）之间急需的知识桥梁。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淋巴丝虫病等疾病。昆虫信息素吸引的分子生理学知识将对我们理解线虫的嗅觉产生直接影响，这最终可以转化为改善对寄生线虫的治疗，估计全球有13亿人受到影响（世卫组织）。我们最近的NIH资助的研究表明，脂质结合蛋白，OBI-1，介导宿主昆虫信息素的传感通过cGMP信号通路，发现在许多动物的感觉细胞。OBI-1属于一类高度保守但功能多样的分泌型脂质结合蛋白，包括哺乳动物中的脂多糖结合蛋白（LBP）、杀菌渗透性增加蛋白（BPI）和胆固醇酯转移蛋白。我们推测，OBI-1的表达，支持化学感觉神经元的胶质细胞所需的线虫的嗅觉器官识别甲虫信息素。我们推测，OBI-1可能作为一个细胞外受体伴侣，引导信息素分子的膜结合受体，或作为一个信号终止剂，以消除信息素从膜结合受体。我们的主要目的是确定OBI-1是否通过神经胶质细胞介导嗅觉，以及OBI-1和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在气味感知过程中如何与cGMP途径的其他因子（如cGMP依赖性蛋白激酶（PKG）EGL-4）发生遗传相互作用。