Signaling pathways for tick salivary secretion

蜱唾液分泌的信号通路

• 批准号: 7948408
• 负责人: Yoonseong Park
• 金额: $ 34.26万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7948408
• 关键词: 3-methoxytyramine; Abbreviations; Acinus organ component; Adenine; Anabolism; Animals; Antibodies; Apical; Arachidonic Acids; Axon; Bacteria; Basal Cell; Benign; Biochemical; Biological Assay; Black-legged Tick; Blood; Carboxy-Lyases; Catecholamines; Cell Nucleus; Cell physiology; Cells; Cloning; Color; Complementary DNA; Crude Extracts; Cyclic AMP; Cytoplasmic Granules; Data; Detection; Development; Dopa; Dopamine; Dopamine Receptor; Economics; Enzyme-Linked Immunosorbent Assay; Enzymes; Epithelial; Epithelial Cells; Event; Expressed Sequence Tags; Female; Figs - dietary; Fluids and Secretions; G Protein-Coupled Receptor Genes; G-Protein-Coupled Receptors; Genes; Health; Hemolymph; High Pressure Liquid Chromatography; Homovanillic Acid; Human; Immune response; In Situ Hybridization; In Vitro; Industry; Investigation; Knowledge; Lead; Ligands; Link; Lyme Disease; Measures; Metabolic; Metabolism; Methods; Molecular; Molecular Cloning; Names; Neurons; Neuropeptide Receptor; Neuropeptides; Neurotransmitters; Osmoregulation; Outcome; Paracrine Communication; Pattern; Peptides; Pharmacology; Phospholipase C; Physiological; Physiology; Play; Polymerase; Protozoa; Publications; RNA Interference; RNA-Directed DNA Polymerase; Race; Reaction; Reporter; Research; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; Salivary; Salivary Glands; Shapes; Side; Signal Pathway; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surface; System; Testing; Tick Control; Tick-Borne Diseases; Ticks; Time; Translating; Tyrosine 3-Monooxygenase; Untranslated Regions; Vaccines; Varicosity; Virus; Whole Organism; Work; base; cell type; design; enzyme activity; feeding; fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; in vivo; mortality; neuromechanism; paracrine; pathogen; public health relevance; receptor; relating to nervous system; response; saliva secretion; tool; vector

DESCRIPTION (provided by applicant): Ticks are obligatory ectoparasites that feed on the blood of vertebrate hosts and often transmit pathogens, including bacteria, protozoa, and viruses. Tick-borne diseases cause huge economic losses in the animal industry as well as health risks to humans. The salivary secretions of ticks play an important role in blood feeding by modulating the host response. We propose to investigate the neural mechanisms controlling salivary secretion in the black-legged tick, Ixodes scapularis, one of the most important ticks in the northern U.S. in terms of its risk to human health. Our preliminary studies, combined with previous studies, led to hypotheses attempting to explain the major mechanism involved in salivary gland control. We hypothesize that myoinhibitory peptide (MIP) and SIFamide control dopamine biosynthesis in the salivary glands. Dopamine, as a paracrine signal synthesized and secreted from basally located cells in the salivary gland acini, activates apical epithelial cells and granular cells in the acini for salivary secretion. To test these hypotheses, three Specific Aims are proposed in this proposal. Specific Aim 1 is to identify and characterize the receptors for each SIFamide and dopamine in the salivary glands. Specific Aim 2 is to investigate the biosynthesis of catecholamines in the salivary glands by biochemical analyses. Specific Aim 3 will be to investigate the functions of MIP, SIFamide, and dopamine signaling pathways in the salivary gland using RNAi and physiological assays. This study will contribute significantly to the body of knowledge that has accumulated in the last three decades with regard to the understanding of the mechanisms controlling the tick salivary gland. The fundamental knowledge obtained from this research is expected to lead to the design of compounds and vaccines that disrupt tick salivary function. The outcome of the proposed research will have a large impact on studies in other tick species that have negative impacts on the economy and human and animal health. PUBLIC HEALTH RELEVANCE: The proposed work will provide an understanding of the mechanism controlling tick salivary gland, which can have large impacts on studies of other tick species that have negative impacts on the economy, and human and animal health. The fundamental knowledge will offer rational approaches to the development of environmentally benign acaricidal compounds.

描述(申请人提供)：扁虱是必需的体外寄生虫，以脊椎动物宿主的血液为食，经常传播包括细菌、原生动物和病毒在内的病原体。壁虱传播的疾病给畜牧业造成了巨大的经济损失，也给人类的健康带来了风险。扁虱的唾液分泌物通过调节宿主的反应，在血液摄取中发挥重要作用。我们建议研究控制黑腿硬蜱唾液分泌的神经机制，就其对人类健康的风险而言，它是美国北部最重要的硬蜱之一。我们的初步研究，结合以前的研究，导致了一些假说，试图解释唾液腺控制的主要机制。我们假设肌肉抑制肽(MIP)和SIF酰胺控制唾液腺中多巴胺的生物合成。多巴胺作为一种旁分泌信号，由涎腺腺泡内的碱基细胞合成和分泌，激活腺泡顶端上皮细胞和颗粒细胞分泌唾液。为了验证这些假设，本提案提出了三个具体目标。具体目标1是识别和表征唾液腺中每种SIF酰胺和多巴胺的受体。具体目标2是通过生化分析研究唾液腺中儿茶酚胺的生物合成。具体目标3将是利用RNAi和生理测试来研究唾液腺中MIP、SIF酰胺和多巴胺信号通路的功能。这项研究将对在过去三十年中积累的关于了解控制扁虱唾液腺的机制的知识体系做出重大贡献。从这项研究中获得的基本知识有望导致设计出扰乱扁虱唾液功能的化合物和疫苗。拟议的研究结果将对对经济以及人类和动物健康产生负面影响的其他扁虱物种的研究产生很大影响。 与公共卫生相关：拟议的工作将提供对控制扁虱唾液腺的机制的了解，这可能会对对经济以及人类和动物健康产生负面影响的其他扁虱物种的研究产生重大影响。基础知识将为开发环境无害的杀螨剂化合物提供合理的方法。