DISSECTING REGULATION OF INTRACELLULAR VESICLE TRAFFICKING IN A TICK SALIVARY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH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 中心，不一定是研究者的机构。 硬蜱的唾液腺（SG）提供了一个令人印象深刻的例子，战略演变的体外寄生虫，以满足其独特的寄生周期的挑战。 在蜱进食过程中，SG分泌大量多余的液体用于血餐浓缩，并分泌调节宿主止血的生物活性蛋白质和脂质化合物。 唾液腺也是病原体传播到宿主的主要途径。 虽然已经鉴定出各种分泌产物，并且已经详细研究了参与调节分泌的几个因素和过程，但令人惊讶的是，对蜱SG中膜融合的分子机制知之甚少。 初步的生理、生物化学、细胞和分子数据表明，在过去难以取得进展的地方，现在可以取得重大的新进展。 具体来说，我们假设，胞吐机制蛋白，如Ykt 6，是重要的唾液中的蛋白质分泌的机制。 鉴于唾液腺的功能多样性，结果应该是相当大的比较感兴趣的细胞分子生物学家研究蛋白质运输分泌组织。 从蜱唾液腺分泌到唾液中的蛋白质是由于受SNARE [可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体]复合物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。 在目前的研究中，我们功能上的特点是一个独特的蜱唾液陷阱蛋白，Ykt 6，以前只知道从哺乳动物神经元细胞，并解剖的分子途径，从唾液腺细胞分泌的关键。

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.