Most salivary proteins are stored in secretion granules prior to export from acinar cells in response to neural stimuli. A small subset of these proteins undergo unstimulated secretion without apparent storage. This pathway probably comprises vesicles that bud from maturing storage granules and carries proteins that do not aggregate efficiently at the storage site. Expression of a parotid proline-rich protein (and deletion mutants) in pituitary AtT-20 cells has shown that an N-terminal domain is necessary for storage in secretion granules. Evidence suggests that self-aggregation of proline-rich protein mediated by this domain may function in both efficient intracellular transport and storage. Thus selective aggregation may be an important secretory sorting mechanism.
References
1.
Ann, D.K., S. Clements, E.M. Johnston, and D.M. Carlson: Induction of Tissue Specific Proline-Rich Protein Multigene Families in Rat and Mouse Parotid Glands by Isoproterenol. Unusual Strain Differences of Proline-Rich Protein mRNAs. J. Biol. Chem. 262:899-904 (1987).
2.
Baranski, T.J., P.L. Faust, and S. Kornfeld: Generation of a Lysosomal Enzyme Targeting Signal in the Secretory Protein Pepsinogen. Cell63:281-291 (1990).
3.
Blair, E.A., A.M. Castle, and J.D. Castle: Proteoglycan Sulfation and Storage Parallels Storage of Basic Secretory Proteins in Exocrine Cells. Am. J. Physiol. 261:C897-C905 (1991).
4.
Burgess, T.L. and R.B. Kelly: Constitutive and Regulated Secretion of Proteins. Annu. Rev. Cell. Biol. 3:243-292 (1987).
5.
Capasso, J.M. and C.B. Hirschberg: Mechanisms of Glycosylation and Sulfation in the Golgi Apparatus: Evidence for Nucleotide Sugar/Nucleoside Monophosphate and Nucleotide Sulfate/Nucleoside Monophosphate Antiports in the Golgi Apparatus Membrane. Proc. Natl. Acad. Sci. U.SA. 81:7051-7055 (1984).
6.
Castle, J.D.: Sorting and Secretory Pathways in Exocrine Cells. Am. J. Resp. Cell Mol. Biol. 2:119-126 (1990).
7.
Chung, K.-N., P. Walter, G.W. Aponte, and H.-P.H. Moore: Molecular Sorting in the Secretory Pathway. Science243:192-197 (1989).
8.
Hashimoto, S., G. Fumagalli, A. Zanini, and J. Meldolesi: Sorting of Three Secretory Proteins to Distinct Secretory Granules in Acidophilic Cells of Cow Anterior Pituitary. J. Cell. Biol. 105:1579-1586 (1987).
9.
Kelly, R.B.: Pathways of Protein Secretion in Eukaryotes. Science230:25-32 (1985).
10.
Kizer, J.S. and A. Tropsha: A Motif Found in Propeptides and Prohormones that May Target Them to Secretory Vesicles. Biochem. Biophys. Res. Commun. 174:586-592 (1991).
11.
Komfeld S. and I. Mellman: The Biogenesis of Lysosomes. Annu. Rev. Cell. Biol. 5:483-525 (1989).
12.
Kousvelari, E.E., F.G. Oppenheim, and L.S. Cutler: Ultrastructural Localization of Salivary Acidic Proline-Rich Proteins from Macaca fascicularis. J. Histochem. Cytochem. 30:274-278 (1982).
13.
Loh, Y.P., Y.P. Tarn, and K. Andreasson: The Signal Involved in Directing Pro-opiomelanocortin into the Regulated Secretory Pathway is Encoded in the N-Terminus of the Prohormone. J. Chem. Biol. 111:319a (1990).
14.
Moore, H.-P., B. Gumbiner, and R.B. Kelly: Chloroquine Diverts ACTH from a Regulated to a Constitutive Secretory Pathway in AtT-20 Cells. Nature (London)302:434-436 (1983a).
15.
Moore, H.-P., B. Gumbiner, and R.B. Kelly: A Subclass of Proteins and Sulfated Macromolecules Secreted by AtT-20 (Mouse Pituitary Tumor) Cells Is Sorted with Adrenocorticotropin into Dense Secretory Granules. J. Cell. Biol. 97:810-817 (1983b).
16.
Moore, H.-P.H. and R.B. Kelly: Re-routing of a Secretory Protein by Fusion with Human Growth Hormone Sequences. Nature321:443-446 (1986).
17.
Muenzer, J., C. Bildstein, M. Gleason, and D.M. Carlson: Purification of Proline-Rich Proteins from Parotid Glands of Isoproterenol-Treated Rats. J. Biol. Chem. 255:5623-5628 (1979 a).
18.
Muenzer, J., C. Bildstein, M. Gleason, and D.M. Carlson: Properties of Proline-Rich Proteins from Parotid Glands of Isoproterenol-Treated Rats. J. Biol. Chem. 254:5629-5634 (1979 b).
19.
Palade, G.E.: Intracellular Aspects of the Process of Protein Synthesis. Science189:347-358 (1975).
20.
Rosa, P., U. Weiss, R. Pepperkok, W. Ansorge, C. Niehrs, E.H.K. Stelzer, and W.B. Huttner: An Antibody Against Secretogranin I (Chromogranin B) Is Packaged into Secretory Granules. J. Cell. Biol. 109:17-34 (1989).
21.
Sossin, W.S., J.M. Fisher, and R.H. Scheller: Sorting within the Regulated Secretory Pathway Occurs in the Trans-Golgi Network. J. Cell. Biol. 110:1-12 (1990).
22.
Stoller, T.J. and D. Shields: The Propeptide of Preprosomatostatin Mediates Intracellular Transport and Secretion of Alpha-Globin from Mammalian Cells. J. Cell. Biol. 108:1647-1656 (1989).
23.
Tooze, J., H.F. Kem, S.D. Fuller, and K.E. Howell: Condensation-Sorting Events in the Rough Endoplasmic Reticulum of Exocrine Pancreatic Cells. J. Cell. Biol. 109:35-50 (1989).
24.
Zastrow, M.V. and J.D. Castle: Protein Sorting among Two Distinct Export Pathways Occurs from the Content of Maturing Exocrine Storage Granules. J. Cell. Biol. 105:2675-2684 (1987).
25.
Zastrow, M.V., A.M. Castle, and J.D. Castle: Ammonium Chloride Alters Secretory Protein Sorting within the Maturing Exocrine Storage Compartment. J. Biol. Chem. 264:6566-6571 (1989).
