Signaling pathways for tick salivary secretion

蜱唾液分泌的信号通路

• 批准号: 8259451
• 负责人: Yoonseong Park
• 金额: $ 29.3万
• 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/8259451
• 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; Reaction; Reporter; Research; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; SHFM1 gene; 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; 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（由申请方提供）：蜱是专性体外寄生虫，以脊椎动物宿主的血液为食，通常传播病原体，包括细菌、原生动物和病毒。蜱传疾病在畜牧业中造成巨大的经济损失，并对人类造成健康风险。蜱的唾液分泌物通过调节宿主反应在吸血中起重要作用。我们建议调查的神经机制控制唾液分泌的黑腿蜱，肩突硬蜱，在北方美国最重要的蜱之一，在其对人类健康的风险。我们的初步研究，结合以前的研究，导致假说试图解释参与唾液腺控制的主要机制。我们推测，肌抑制肽（MIP）和SIFamide控制多巴胺在唾液腺的生物合成。多巴胺作为一种旁分泌信号，由位于涎腺腺泡底部的细胞合成和分泌，激活腺泡顶端上皮细胞和颗粒细胞进行唾液分泌。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是鉴定和表征唾液腺中每种SIFamide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将是研究MIP，SIFamide和多巴胺信号通路在唾液腺中的功能，使用RNAi和生理测定。这项研究将大大有助于身体的知识，积累了在过去的三十年里，关于控制蜱唾液腺的机制的理解。从这项研究中获得的基础知识有望导致破坏蜱唾液功能的化合物和疫苗的设计。拟议研究的结果将对其他蜱虫物种的研究产生重大影响，这些蜱虫物种对经济以及人类和动物健康产生负面影响。 公共卫生关系：拟议的工作将提供控制蜱唾液腺的机制的理解，这可能对其他蜱物种的研究产生重大影响，这些蜱物种对经济，人类和动物健康产生负面影响。这些基础知识将为开发环境友好的杀螨化合物提供合理的途径。