Chronic drug use affects peptide production in many cells, thus it is important to understand mechanisms for regulation of peptide production. Although the enzymes which catalyze processing of large inactive precursors into bioactive peptides are well established, many proteins and events which regulate synthesis, routing, and secretion of peptides remain elusive. The tissue distribution, cellular localization, and regulation of a novel protein, RESP18 (regulated endocrine specific protein, 18 Kda) suggest a function important to the regulation of, or biosynthesis of peptides. RESP18 is a novel protein identified by virtue of its regulation by dopaminergic input in the intermediate pituitary lobe in parallel with the hormone precursor, proopiomelanocortin (POMC), and several proteins which facilitate the maturation of POMC into bioactive peptides {105,240}. RESP18 is found in cells of all major endocrine glands that secrete bioactive peptides. RESP18 is unique as a neuroendocrine-specific luminal endoplasmic reticulum (ER) resident protein. Preliminary data suggested that the synthesis and routing of POMC and an endoprotease that processes POMC, PC1, were repressed. This proposal will establish a system with inducible RESP18 expression to assess the effect of RESP18 on the synthesis, routing, processing, and secretion of POMC, PC1 and several other cellular proteins. Using this expression system I will analyze the extent and specificity of RESP18 induction on the several protein with functions and localizations other than POMC and PC1. Results from this analysis will be used explore the mechanism by which RESP18 elicits these effects.
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| Ciccotosto, G D; Schiller, M R; Eipper, B A et al. (1999) Induction of integral membrane PAM expression in AtT-20 cells alters the storage and trafficking of POMC and PC1. J Cell Biol 144:459-71 |
| Schiller, M R; Mains, R E; Eipper, B A (1997) A novel neuroendocrine intracellular signaling pathway. Mol Endocrinol 11:1846-57 |
