title: The major zymogen granule membrane protein GP-2 in the rat pancreas is not involved in granule formation.
abstract: The major membrane protein of zymogen granules in the rat pancreas is a glycoprotein of 78 kDa (GP-2), which is inserted into the membrane via a glycosyl-phosphatidylinositol (GPI) anchor. GP-2 occurs in both, a membrane-attached and a soluble form. Due to its specific luminal orientation and its quantitative contribution to the zymogen granule membrane, GP-2 has been postulated to play an important role in sorting of digestive enzymes into the granule and in the formation of the granule as a storage organelle. We have tested this hypothesis in the rat pancreas under three different functional conditions, where both the rates of enzyme/isoenzyme synthesis change drastically, and new zymogen granules form at a high rate: a) during prolonged hormonal stimulation of the adult rat pancreas, b) during the differentiation of AR4-2J cells induced by dexamethasone in vitro, and c) during embryonic development and early postnatal life, when gene expression is modulated due to the differentiation program. Both, GP-2 mRNA levels and the rate of GP-2 biosynthesis were quantitated and compared to the immunohistochemical localization of this protein in tissue sections. Under all three functional conditions, significant changes could be demonstrated at the level of digestive enzyme gene expression, but no concomitant modulation of GP-2 expression was observed. GP-2 mRNA is absent from the embryonic pancreas and for the first time is expressed after birth with a significant increase during the period of weaning. Furthermore, GP-2 mRNA and protein levels are not modulated by hormonal stimulation, either in the adult pancreas or in AR4-2J cells in culture. Therefore, we conclude that GP-2, in spite of its quantitative contribution to the zymogen granule membrane, is not involved in enzyme protein sorting or granule formation. Alternative functions for GP-2 are discussed.
authors.affiliation: Department of Cell Biology and Cell Pathology, Philipps University, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Dittié
authors.forename: H F
authors.initials: HF
authors.lastname: Kern
mesh_terms: D000681:Amylases / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000737:chemistry*; D003907:Dexamethasone / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D015870:Gene Expression; D015151:Immunoblotting; D007425:Intracellular Membranes / Q000737:chemistry*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004792:Enzyme Precursors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C072961:glycoprotein-2, pancreas; D003907:Dexamethasone; D000681:Amylases