Localization of Secretion-Related Proteins in Pancreatic

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Molecular mechanisms of regulated exocytosis involving the endocrine-specific protein Resp18 are not yet fully understood. Resp18 was first isolated from a rat pituitary cDNA library in a search for genes that are regulated by dopaminergic drugs. Previously, it has been believed that RESP18 is localized primarily in the endoplasmic reticulum (ER) of neuroendocrine tissues. Since part of RESP18 shares a sequence homology with the luminal region of IA-2, a dense-core vesicle membrane protein involved in vesicle stabilization and biosynthesis, we have tested the hypothesis that RESP18 is implicated in the regulation of dense-core vesicle secretion. Using immuno electron microcopy, we find that RESP18 is mainly expressed in the lumen of DCVs and only to a lesser extent in the ER and Golgi network. Furthermore, double labeling experiments demonstrate that RESP18 is colocalized with insulin in pancreatic beta cell vesicles, as well as with glucagon in pancreatic alpha cell vesicles. The results suggest that RESP18 is a novel luminal protein of regulated secretory vesicles involving the regulated insulin secretion signaling pathway.