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J Cell Biol. 1989 Jul 1; 109(1): 35–50.
PMCID: PMC2115466

Condensation-sorting events in the rough endoplasmic reticulum of exocrine pancreatic cells


In guinea pig exocrine pancreatic cells intracisternal granules (ICGs) occur at a low frequency within the lumen of the RER. By starving and refeeding guinea pigs or injecting them in CoCl2 solution, the number of these granules is greatly increased. We show here that ICGs contain the complete set of secreted pancreatic digestive enzymes and proenzymes. Two other soluble proteins in the lumen of the RER, GRP 78/BiP and protein disulphide isomerase (PDI), are specifically excluded from ICGs. The formation of ICGs, which occurs without acidification of the RER cisternae, is therefore a sorting event involving the cocondensation of a complete set of secretory enzymes and proenzymes, which for brevity we refer to collectively as the zymogens. With the exception of approximately 50% of the RNase, the zymogens in ICGs are covalently cross-linked by intermolecular disulphide bonds. The synthesis of all three resident ER cisternal proteins--PDI, GRP 78/BiP, and GRP 94--with the carboxy-terminal sequence KDEL, is induced in response to the accumulation of massive amounts of misfolded secretory protein in the ICGs in the lumen of the RER. After injection of rats with large doses of parachlorophenylalanine-methylester, crystals form in the lumen of the RER. We show that these crystals appear to be a lattice of amylase with the other zymogens incorporated between the layers. Both GRP 78/BiP and PDI are excluded from these crystals. The formation of these amylase crystals within the RER and the inclusion of other zymogens is, therefore, also a sorting event. These data establish that in exocrine pancreatic cells zymogens can cocondense in the RER into either amorphous aggregates or crystals that exclude other soluble RER proteins. This demonstrates that cocondensation is a mechanism capable of sorting zymogens within the secretory pathway.

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Selected References

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  • Anderson RG, Pathak RK. Vesicles and cisternae in the trans Golgi apparatus of human fibroblasts are acidic compartments. Cell. 1985 Mar;40(3):635–643. [PubMed]
  • Anderson RG, Falck JR, Goldstein JL, Brown MS. Visualization of acidic organelles in intact cells by electron microscopy. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4838–4842. [PMC free article] [PubMed]
  • Balch WE, Elliott MM, Keller DS. ATP-coupled transport of vesicular stomatitis virus G protein between the endoplasmic reticulum and the Golgi. J Biol Chem. 1986 Nov 5;261(31):14681–14689. [PubMed]
  • Bendayan M, Roth J, Perrelet A, Orci L. Quantitative immunocytochemical localization of pancreatic secretory proteins in subcellular compartments of the rat acinar cell. J Histochem Cytochem. 1980 Feb;28(2):149–160. [PubMed]
  • Bieger W, Kern HF. Studies on intracellular transport in the rat exocrine pancreas. I. Inhibition by aromatic amino acids in vitro. Virchows Arch A Pathol Anat Histol. 1975 Sep 18;367(4):289–305. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Broadwell RD, Oliver C. Golgi apparatus, GERL, and secretory granule formation within neurons of the hypothalamo-neurohypophysial system of control and hyperosmotically stressed mice. J Cell Biol. 1981 Aug;90(2):474–484. [PMC free article] [PubMed]
  • Burgess TL, Kelly RB. Constitutive and regulated secretion of proteins. Annu Rev Cell Biol. 1987;3:243–293. [PubMed]
  • Burnette WN. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. [PubMed]
  • Case RM. Synthesis, intracellular transport and discharge of exportable proteins in the pancreatic acinar cell and other cells. Biol Rev Camb Philos Soc. 1978 May;53(2):211–354. [PubMed]
  • Creighton TE. Experimental studies of protein folding and unfolding. Prog Biophys Mol Biol. 1978;33(3):231–297. [PubMed]
  • Farquhar MG, Palade GE. The Golgi apparatus (complex)-(1954-1981)-from artifact to center stage. J Cell Biol. 1981 Dec;91(3 Pt 2):77s–103s. [PMC free article] [PubMed]
  • Forssmann WG, Bieger W. Biosynthese falscher Proteine: Einbau von p-Chlorphenylalanin in Enzyme des exokrinen Pankreas. Res Exp Med (Berl) 1973 Mar 14;160(1):1–20. [PubMed]
  • Geuze HJ, Slot JW. Disproportional immunostaining patterns of two secretory proteins in guinea pig and rat exocrine pancreatic cells. An immunoferritin and fluorescence study. Eur J Cell Biol. 1980 Apr;21(1):93–100. [PubMed]
  • Griffiths G, McDowall A, Back R, Dubochet J. On the preparation of cryosections for immunocytochemistry. J Ultrastruct Res. 1984 Oct;89(1):65–78. [PubMed]
  • Hopkins CR. The biosynthesis, intracellular transport, and packaging of melanocyte-stimulating peptides in the amphibian pars intermedia. J Cell Biol. 1972 Jun;53(3):642–653. [PMC free article] [PubMed]
  • Jamieson JD, Palade GE. Intracellular transport of secretory proteins in the pancreatic exocrine cell. IV. Metabolic requirements. J Cell Biol. 1968 Dec;39(3):589–603. [PMC free article] [PubMed]
  • Kassenbrock CK, Garcia PD, Walter P, Kelly RB. Heavy-chain binding protein recognizes aberrant polypeptides translocated in vitro. Nature. 1988 May 5;333(6168):90–93. [PubMed]
  • Kern HF, Kern D. Elektronenmikroskopische Untersuchungen über die Wirkung von Kobaltchlorid auf das exokrine Pankreasgewebe des Meerschweinchens. Virchows Arch B Cell Pathol. 1969;4(1):54–70. [PubMed]
  • Kozutsumi Y, Segal M, Normington K, Gething MJ, Sambrook J. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature. 1988 Mar 31;332(6163):462–464. [PubMed]
  • Kreis TE. Microinjected antibodies against the cytoplasmic domain of vesicular stomatitis virus glycoprotein block its transport to the cell surface. EMBO J. 1986 May;5(5):931–941. [PMC free article] [PubMed]
  • Lambert N, Freedman RB. Structural properties of homogeneous protein disulphide-isomerase from bovine liver purified by a rapid high-yielding procedure. Biochem J. 1983 Jul 1;213(1):225–234. [PMC free article] [PubMed]
  • Louvard D, Reggio H, Warren G. Antibodies to the Golgi complex and the rough endoplasmic reticulum. J Cell Biol. 1982 Jan;92(1):92–107. [PMC free article] [PubMed]
  • Macer DR, Koch GL. Identification of a set of calcium-binding proteins in reticuloplasm, the luminal content of the endoplasmic reticulum. J Cell Sci. 1988 Sep;91(Pt 1):61–70. [PubMed]
  • McPherson A, Rich A. X-ray crystallographic analysis of swine pancreas -amylase. Biochim Biophys Acta. 1972 Dec 28;285(2):493–497. [PubMed]
  • Merisko EM, Fletcher M, Palade GE. The reorganization of the Golgi complex in anoxic pancreatic acinar cells. Pancreas. 1986;1(2):95–109. [PubMed]
  • Munro S, Pelham HR. An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell. 1986 Jul 18;46(2):291–300. [PubMed]
  • Munro S, Pelham HR. A C-terminal signal prevents secretion of luminal ER proteins. Cell. 1987 Mar 13;48(5):899–907. [PubMed]
  • Orci L, Ravazzola M, Anderson RG. The condensing vacuole of exocrine cells is more acidic than the mature secretory vesicle. Nature. 1987 Mar 5;326(6108):77–79. [PubMed]
  • PALADE GE. Intracisternal granules in the exocrine cells of the pancreas. J Biophys Biochem Cytol. 1956 Jul 25;2(4):417–422. [PMC free article] [PubMed]
  • Pelham HR. Evidence that luminal ER proteins are sorted from secreted proteins in a post-ER compartment. EMBO J. 1988 Apr;7(4):913–918. [PMC free article] [PubMed]
  • Peters T, Jr, Davidson LK. The biosynthesis of rat serum albumin. In vivo studies on the formation of the disulfide bonds. J Biol Chem. 1982 Aug 10;257(15):8847–8853. [PubMed]
  • Rall L, Pictet R, Githens S, Rutter WJ. Glucocorticoids modulate the in vitro development of the embryonic rat pancreas. J Cell Biol. 1977 Nov;75(2 Pt 1):398–409. [PMC free article] [PubMed]
  • Rausch U, Vasiloudes P, Rüdiger K, Kern HF. In-vivo stimulation of rat pancreatic acinar cells by infusion of secretin. II. Changes in individual rates of enzyme and isoenzyme biosynthesis. Cell Tissue Res. 1985;242(3):641–644. [PubMed]
  • Reggio H, Dagorn JC. Ionic interactions between bovine chymotrypsinogen A and chondroitin sulfate A.B.C.. A possible model for molecular aggregation in zymogen granules. J Cell Biol. 1978 Sep;78(3):951–957. [PMC free article] [PubMed]
  • Reggio HA, Palade GE. Sulfated compounds in the zymogen granules of the guinea pig pancreas. J Cell Biol. 1978 May;77(2):288–314. [PMC free article] [PubMed]
  • Salpeter MM, Farquhar MG. High resolution analysis of the secretory pathway in mammotrophs of the rat anterior pituitary. J Cell Biol. 1981 Oct;91(1):240–246. [PMC free article] [PubMed]
  • Scheele GA. Two-dimensional gel analysis of soluble proteins. Charaterization of guinea pig exocrine pancreatic proteins. J Biol Chem. 1975 Jul 25;250(14):5375–5385. [PubMed]
  • Scheele GA, Palade GE. Studies on the guinea pig pancreas. Parallel discharge of exocrine enzyme activities. J Biol Chem. 1975 Apr 10;250(7):2660–2670. [PubMed]
  • Schick J, Kern H, Scheele G. Hormonal stimulation in the exocrine pancreas results in coordinate and anticoordinate regulation of protein synthesis. J Cell Biol. 1984 Nov;99(5):1569–1574. [PMC free article] [PubMed]
  • Seybold J, Bieger W, Kern HF. Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. II. Inhibition of antimicrotubular agents. Virchows Arch A Pathol Anat Histol. 1975 Nov 28;368(4):309–327. [PubMed]
  • Tartakoff AM, Jamieson JD. Subcellular fractionation of the pancreas. Methods Enzymol. 1974;31:41–59. [PubMed]
  • Tokuyasu KT. Immunochemistry on ultrathin frozen sections. Histochem J. 1980 Jul;12(4):381–403. [PubMed]
  • Wichman A, Svenson A, Andersson LO. Kinetics of refolding of completely reduced human-serum albumin. Regain of immunochemical reactivity. Eur J Biochem. 1977 Oct 3;79(2):339–344. [PubMed]

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