Overexpression of Rab3D Enhances Regulated Amylase Secretion from Pancreatic

Rab3D, a member of the ras-related GTP-binding protein Rab family, is localized to secretory granules of various exo-crine tissues such as acinar cells of the pancreas, chief cells of the stomach, and parotid and lacrimal secretory cells. To elucidate the function of Rab3D in exocytosis, we have gen-erated transgenic mice that over-express Rab3D specifically in pancreatic acinar cells. Hemagglutinin-tagged Rab3D was localized to zymogen granules by immunohistochemistry, and was shown to be present on zymogen granule membranes by Western blotting; both results are similar to previous studies of endogenous Rab3D. Secretion measurements in isolated acinar preparations showed that overexpression of Rab3D enhanced amylase release. Amylase secretion from intact acini of transgenic mice 5 min after 10 pM cholecystokinin octapeptide (CCK) stimulation was enhanced by 160 % of control. In streptolysin-O–permeabilized acini of transgenic mice, amylase secretion induced by 100