The Secretory Mechanisms and Dysfunction Section investigates the molecular nature and function of the ion transport mechanisms involved in the fluid and electrolyte secretion process in the exocrine salivary gland. We are probing the structure-function relationships of cotransporter, exchanger and channel proteins using a combination of molecular biology, gene modification, proteomics and functional studies in mouse and human salivary glands. We are using a high-throughput approach to catalogue the human saliva proteome, to identify salivary biomarkers for human diseases, and to compile a comprehensive list of the plasma membrane proteins expressed in salivary glands. Accomplishments/conclusions: Mice lacking ClC-2 channels have a severe defect in absorptive ion transport in the distal colon. This is the first demonstration of the function of ClC-2 in NaCl absorption. We performed a quantitative salivary proteomic survey of patients with chronic Graft-versus-Host Disease (cGvHD). Clear differences were observed in the saliva of cGvHD patients with oral manifestations compared to those with no oral pathology. A quantitative proteomic analysis of parotid saliva revealed differences in expression consistent with the immunological disease status of Primary Sjgrens Syndrome patients. The TRPV4 receptor-channel was found to modulate Ca2+ influx in acinar cells and to stimulate salivation in the mouse submandibular gland. As part of a team effort, a quantitative model of electrolyte exchange was developed that can explain salivary ductal function.
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