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

基本信息

批准号：
9086371
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
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9086371
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

项目摘要

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物种是与特定甲虫相关的线虫，代表了一种被称为死亡的线虫 - 互动率很高但高度普遍的类型，称为Necromeny。 pristionchus线虫如何保持特定昆虫相互作用的工作模型是拦截其宿主昆虫的内在通信。鉴于众多的线虫与昆虫和哺乳动物宿主的关联，甲虫相关的Pristionchus Pacificus代表了自由生活模型有机体Caenorhabditis elegans和人类丝状线虫（如Brugia Malayi和Wucheria bancrofti）之间急需的知识桥梁。这与人类健康尤其重要，因为丝状线虫还需要昆虫向量传播诸如淋巴丝虫病之类的疾病。了解昆虫信息素吸引力的分子生理学将对我们对线虫中的嗅觉的理解产生直接影响，这最终可以转化为改善针对寄生虫的治疗方法，这些寄生虫遭受了估计估计有13亿人（WHO）的13亿人。我们最近由NIH资助的研究表明，脂质结合蛋白OBI-1通过CGMP信号传导途径介导宿主的昆虫信息素传感，这在许多动物的感觉细胞中都发现。 OBI-1属于一类高度保守但功能多样的分泌脂质结合蛋白，包括脂多糖结合蛋白（LBPS），杀菌性通透性 - 增强蛋白（BPIS）和胆汁含量的蛋白质和胆汁脂蛋白酯的转移蛋白。我们假设线虫的嗅觉器官需要OBI-1在神经胶质细胞中支持化学感应神经元的表达才能识别甲虫的信息素。我们推测，OBI-1可以充当细胞外受体伴侣伴侣，以指导到膜结合受体的信息素分子，或者作为信号终结剂，以从膜结合受体中去除信息素。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与信息素分子之间存在直接相互作用。我们的长期重点是询问OBI-1在气味传感期间CGMP途径（例如CGMP依赖性蛋白激酶（PKG）EGL-4）与其他因素相互作用。