DISSECTING REGULATION OF INTRACELLULAR VESICLE TRAFFICKING IN A TICK SALIVARY

剖析蜱唾液中细胞内囊泡运输的调节

• 批准号: 7609975
• 负责人: Shahid Karim
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609975
• 关键词: Binding; Binding Proteins; Biochemical; Black-legged Tick; Blood; Cell membrane; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Critical Pathways; Data; Exocytosis; Funding; Grant; Hemostatic function; Institution; Lipids; Liquid substance; Membrane; Membrane Fusion; Molecular; Neurons; Physiological; Process; Protein Secretion; Proteins; Regulation; Research; Research Personnel; Resources; Role; Route; SNAP receptor; Saliva; Salivary; Salivary Glands; Secretory Vesicles; Source; Ticks; Tissues; United States National Institutes of Health; Vesicle; Work; comparative; feeding; interest; intracellular protein transport; pathogen; protein transport; receptor; trafficking; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The salivary glands (SG) of ixodid ticks provide an impressive example of strategies evolved in an ectoparasite to meet the challenge of its unique parasitic cycle. During tick feeding, SG excrete copious amounts of excess fluid for blood-meal concentration, and secrete bioactive protein and lipid compounds which modulate host hemostasis. Salivary glands also are the major route for pathogen transmission to hosts. Although various secretory products have been identified, and several factors and processes involved in regulating secretion have been studied in some detail surprisingly little is known about the molecular mechanism of membrane fusion in tick SG. Preliminary physiological, biochemical, cellular and molecular data suggest that significant new progress can now be made where progress in the past has been difficult. Specifically, we hypothesize that exocytotic machinery proteins, like Ykt6, are important to the mechanism of protein secretion in saliva. Given the salivary glands functional diversity, results should be of considerable comparative interest to cell molecular biologists studying protein trafficking in secretory tissues. Protein secretion into the saliva from the tick salivary glands is due to exocytosis of vesicular membrane bound granular material regulated by SNARE [soluble N-ethylmaleimide-sensitive factor attachment protein receptor] complex proteins. Our work to date has demonstrated the role of selected vesicle and plasma membrane-bound protein receptors (SNAREs) in regulating protein secretion in tick salivary gland cells. Our working hypothesis is that SNARE proteins regulate secretion of immuno-modulatory factors from secretory vesicles into tick saliva. In the current study, we functionally characterize a unique tick salivary SNARE protein, Ykt6, formerly known only from mammalian neuronal cells, and dissect the molecular pathway critical to secretion from salivary gland cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 蜱虫的唾液腺（SG）提供了一个令人印象深刻的例子，说明了外寄生虫为了应对其独特的寄生周期的挑战而进化出的策略。 在蜱进食期间，SG 会分泌大量多余的液体以提高血粉浓度，并分泌调节宿主止血的生物活性蛋白和脂质化合物。 唾液腺也是病原体传播给宿主的主要途径。 尽管已经鉴定出各种分泌产物，并且对涉及调节分泌的几种因素和过程进行了一些详细的研究，但令人惊讶的是，人们对蜱 SG 膜融合的分子机制知之甚少。 初步的生理、生化、细胞和分子数据表明，在过去难以取得进展的领域，现在可以取得重大的新进展。 具体来说，我们假设胞吐机器蛋白（如 Ykt6）对于唾液中蛋白质分泌的机制很重要。 考虑到唾液腺的功能多样性，研究分泌组织中蛋白质运输的细胞分子生物学家应该对结果具有相当大的兴趣。 蜱唾液腺中的蛋白质分泌到唾液中是由于 SNARE（可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体）复合蛋白调节的囊泡膜结合颗粒物质的胞吐作用。迄今为止，我们的工作已经证明了选定的囊泡和质膜结合蛋白受体（SNARE）在调节蜱唾液腺细胞蛋白质分泌中的作用。 我们的工作假设是 SNARE 蛋白调节免疫调节因子从分泌囊泡分泌到蜱唾液中。 在当前的研究中，我们对一种独特的蜱唾液 SNARE 蛋白 Ykt6 进行了功能表征，该蛋白以前仅来自哺乳动物神经元细胞，并剖析了对唾液腺细胞分泌至关重要的分子途径。