Signaling pathways for tick salivary secretion

蜱唾液分泌的信号通路

• 批准号: 8460912
• 负责人: Yoonseong Park
• 金额: $ 27.55万
• 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/8460912
• 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.

描述（由申请人提供）：蜱虫是强制性的体外寄生虫，以脊椎动物宿主的血液为食，经常传播病原体，包括细菌、原生动物和病毒。蜱传疾病给畜牧业造成了巨大的经济损失，也给人类带来了健康风险。蜱的唾液分泌物通过调节宿主的反应在供血中起着重要的作用。我们拟对美国北部最重要的蜱类之一——肩胛骨黑足蜱（Ixodes scapularis）唾液分泌的神经机制及其对人类健康的危害进行研究。我们的初步研究结合以往的研究，提出了一些假说，试图解释唾液腺控制的主要机制。我们假设肌抑制肽（MIP）和SIFamide控制唾液腺中多巴胺的生物合成。多巴胺是唾液腺腺泡中基部细胞合成分泌的旁分泌信号，激活腺泡中的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。具体目的1是鉴定和表征唾液腺中每种SIFamide和多巴胺的受体。具体目的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和生理分析研究唾液腺中MIP、SIFamide和多巴胺信号通路的功能。这项研究将有助于显著的知识体，积累了在过去的三十年中，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设计破坏蜱虫唾液功能的化合物和疫苗。拟议研究的结果将对对经济、人类和动物健康产生负面影响的其他蜱类的研究产生重大影响。