This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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