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Posttranslational Processing of Gut Peptides

Chris Dickinson, Tadataka Yamada

10.1002/cphy.cp060203

Source: Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Initial Events in Peptide Synthesis
2 Processing in the Endoplasmic Reticulum
3 Processing in the Golgi Complex
4 Processing in Secretory Vesicles
4.1 Acetylation
4.2 Dibasic Cleavage
4.3 Monobasic Cleavage
4.4 Amidation
5 Posttranslational Processing of Progastrin
Figure 1. Figure 1.

Signal peptide hypothesis. A: ribosome binds to mRNA and translation begins. B: signal sequence emerges from ribosome and binds to signal recognition particle (SRP), which induces translational arrest. C: SRP‐ribosome complex binds to SRP receptor or docking protein located on rough endoplasmic reticulum (RER) membrane. D: with release of SRP, translation resumes and precursor is translocated into RER cistern in aqueous environment, presumably via a protein pore. E: signal peptide is cleaved by a signal peptidase. F: translation continues until entire precursor is located within RER. G: translation ends and ribosome disassociates from mRNA.
Figure 2. Figure 2.

Intracellular location of posttranslational processing steps.
Figure 3. Figure 3.

Structure of preproinsulin. A‐chain and B‐chain are initially linked by intramolecular disulfide bonds (*), but after connecting peptide is removed by proteolytic cleavage, disulfide bonds become intermolecular.
Figure 4. Figure 4.

Thin sections of rat β‐cells stained with monoclonal antibody to proinsulin or with anticlathrin serum. A: proinsulin immunolabeling revealed by gold particles occurs on Golgi stacks (G) and in a population of secretory granules (filled arrowheads). Labeled granules are associated with Golgi area and characterized by tightly fitting cores. Proinsulin‐rich granules are also characteristically coated (inset, broken line). Other granule population (open arrowheads), characterized by a peripheral halo and lacking coats, is very weakly labeled. This population reacts intensely with anti‐insulin serum. B: clathrin immunolabeling of several secretory granules with tightly fitting cores. Arrows, gold particles revealing clathrin antigenic sites. Clathrin immunoreactivity (inset, arrows) is also detected on trans‐Golgi cisternae with condensing secretory materials. C, D: consecutive serial sections immunostained for clathrin to show the limited three‐dimensional extension of labeled (coated) segments on individual granules with tightly fitting cores (1–3). A: × 23,000; inset, × 83,000. B: × 52,000; inset, × 44,000. C, D: × 28,000.

From Orci et al. 100
Figure 5. Figure 5.

Field of β‐cell cytoplasm immunostained with anti‐insulin serum. Unlike proinsulin monoclonal antibody, insulin serum, which reveals insulin antigenic sites but cross‐reacts with proinsulin, labels all secretory granules either with tightly fitting cores (filled arrowheads) or with peripheral halos (open arrowheads). G, labeled Golgi stack. × 42,000.

From Orci et al. 97
Figure 6. Figure 6.

Endopeptidase cleavage hypothesis involves trypsin‐like cleavage on the COOH‐terminal side of a dibasic pair. This is followed by a carboxypeptidase B‐like cleavage of remaining basic residues.
Figure 7. Figure 7.

Proline‐directed arginyl cleavage and other monobasic cleavage sites in precursors of regulatory peptides. Relevant peptide product is indicated by a hatched bar, and the name is written to the left. Prolines situated adjacent to target arginines are circled. Vertical arrows, peptide bond that is suggested initially to be attacked by an endopeptidase (except in the case of dynorphin B where cleavage point is indicated by long curved arrow). Short curved arrows, following action of the carboxypeptidase B‐like enzyme. Glycine residues, which subsequently will serve as the nitrogen donor during the formation of an α‐carboxyamide group on the final bioactive peptide, have been put in separate hatched bars.

From Schwartz 115
Figure 8. Figure 8.

Peptide α‐amidation monooxygenase converts a glycine‐extended precursor into a COOH‐terminally amidated peptide and glyoxalate. Nitrogen of glycine extension becomes nitrogen in peptide amide.
Figure 9. Figure 9.

Immunohistochemical localization of gastrin, G‐Gly, and progastrin in porcine antral mucosal cells. Single sections of antral mucosa were labeled by immunofluorescence followed by immunoperoxidase techniques with two different antibodies. Panels A and B: same section labeled by immunofluorescence for gastrin (B) and by immunoperoxidase for progastrin (A). Panels C and D: labeled for G‐Gly (D) and progastrin (C). Panels E and F: labeled for gastrin (F) and G‐Gly (E). Numbers, labeled sections. Micrographs indicate that gastrin, G‐Gly, and progastrin are colocalized in antral mucosal G cells.

From Sugano et al. 129
Figure 10. Figure 10.

Pathways for posttranslational processing of gastrin.


Figure 1.

Signal peptide hypothesis. A: ribosome binds to mRNA and translation begins. B: signal sequence emerges from ribosome and binds to signal recognition particle (SRP), which induces translational arrest. C: SRP‐ribosome complex binds to SRP receptor or docking protein located on rough endoplasmic reticulum (RER) membrane. D: with release of SRP, translation resumes and precursor is translocated into RER cistern in aqueous environment, presumably via a protein pore. E: signal peptide is cleaved by a signal peptidase. F: translation continues until entire precursor is located within RER. G: translation ends and ribosome disassociates from mRNA.



Figure 2.

Intracellular location of posttranslational processing steps.



Figure 3.

Structure of preproinsulin. A‐chain and B‐chain are initially linked by intramolecular disulfide bonds (*), but after connecting peptide is removed by proteolytic cleavage, disulfide bonds become intermolecular.



Figure 4.

Thin sections of rat β‐cells stained with monoclonal antibody to proinsulin or with anticlathrin serum. A: proinsulin immunolabeling revealed by gold particles occurs on Golgi stacks (G) and in a population of secretory granules (filled arrowheads). Labeled granules are associated with Golgi area and characterized by tightly fitting cores. Proinsulin‐rich granules are also characteristically coated (inset, broken line). Other granule population (open arrowheads), characterized by a peripheral halo and lacking coats, is very weakly labeled. This population reacts intensely with anti‐insulin serum. B: clathrin immunolabeling of several secretory granules with tightly fitting cores. Arrows, gold particles revealing clathrin antigenic sites. Clathrin immunoreactivity (inset, arrows) is also detected on trans‐Golgi cisternae with condensing secretory materials. C, D: consecutive serial sections immunostained for clathrin to show the limited three‐dimensional extension of labeled (coated) segments on individual granules with tightly fitting cores (1–3). A: × 23,000; inset, × 83,000. B: × 52,000; inset, × 44,000. C, D: × 28,000.

From Orci et al. 100


Figure 5.

Field of β‐cell cytoplasm immunostained with anti‐insulin serum. Unlike proinsulin monoclonal antibody, insulin serum, which reveals insulin antigenic sites but cross‐reacts with proinsulin, labels all secretory granules either with tightly fitting cores (filled arrowheads) or with peripheral halos (open arrowheads). G, labeled Golgi stack. × 42,000.

From Orci et al. 97


Figure 6.

Endopeptidase cleavage hypothesis involves trypsin‐like cleavage on the COOH‐terminal side of a dibasic pair. This is followed by a carboxypeptidase B‐like cleavage of remaining basic residues.



Figure 7.

Proline‐directed arginyl cleavage and other monobasic cleavage sites in precursors of regulatory peptides. Relevant peptide product is indicated by a hatched bar, and the name is written to the left. Prolines situated adjacent to target arginines are circled. Vertical arrows, peptide bond that is suggested initially to be attacked by an endopeptidase (except in the case of dynorphin B where cleavage point is indicated by long curved arrow). Short curved arrows, following action of the carboxypeptidase B‐like enzyme. Glycine residues, which subsequently will serve as the nitrogen donor during the formation of an α‐carboxyamide group on the final bioactive peptide, have been put in separate hatched bars.

From Schwartz 115


Figure 8.

Peptide α‐amidation monooxygenase converts a glycine‐extended precursor into a COOH‐terminally amidated peptide and glyoxalate. Nitrogen of glycine extension becomes nitrogen in peptide amide.



Figure 9.

Immunohistochemical localization of gastrin, G‐Gly, and progastrin in porcine antral mucosal cells. Single sections of antral mucosa were labeled by immunofluorescence followed by immunoperoxidase techniques with two different antibodies. Panels A and B: same section labeled by immunofluorescence for gastrin (B) and by immunoperoxidase for progastrin (A). Panels C and D: labeled for G‐Gly (D) and progastrin (C). Panels E and F: labeled for gastrin (F) and G‐Gly (E). Numbers, labeled sections. Micrographs indicate that gastrin, G‐Gly, and progastrin are colocalized in antral mucosal G cells.

From Sugano et al. 129


Figure 10.

Pathways for posttranslational processing of gastrin.

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Article Title: Posttranslational Processing of Gut Peptides
 

How to Cite

Chris Dickinson, Tadataka Yamada. Posttranslational Processing of Gut Peptides. Compr Physiol 2011, Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology: 63-77. First published in print 1989. doi: 10.1002/cphy.cp060203