pH-independent and -dependent cleavage of proinsulin in the same secretory vesicle

doi:10.1083/jcb.126.5.1149

This Article

Full Text (PDF, 2700K)

Alert me when this article is cited

Citation Map

Services

Email this article

Similar articles in this journal

Similar articles in PubMed

Alert me to new content in the JCB

Download to citation manager

Citing Articles

Citing Articles via HighWire

Citing Articles via CrossRef

Citing Articles via Google Scholar

Google Scholar

Articles by Orci, L.

Articles by Anderson, R. G.

Search for Related Content

PubMed

PubMed Citation

Articles by Orci, L.

Articles by Anderson, R. G.

Pubmed/NCBI databases

Hazardous Substances DB
Compound via MeSH
Substance via MeSH
AMMONIUM CHLORIDE
GLUCOSE

Social Bookmarking

What's this?

ARTICLES

pH-independent and -dependent cleavage of proinsulin in the same secretory vesicle

L Orci, P Halban, A Perrelet, M Amherdt, M Ravazzola and RG Anderson
Departement de Morphologie, University of Geneva, Switzerland.

By quantitative immunoelectron microscopy and HPLC, we have studied the effect of disrupting pH gradients, by ammonium chloride, on proinsulin conversion in the insulin-producing B-cells of the islets of langerhans. Proinsulin content and pH in single secretory vesicles were measured on consecutive serial sections immunostained alternately with anti-proinsulin or anti-dinitrophenol (to reveal the pH-sensitive probe DAMP) antibodies. Radioactivity labeled proinsulin, proinsulin cleavage intermediates, and insulin were quantitated by HPLC analysis of extracts of islets treated in the same conditions. Cleavage at the C- peptide/A-chain junction is significantly less sensitive to pH gradient disruption than that of the B-chain/C-peptide junction, but the range of pH and proinsulin content in individual vesicles indicate that both cleavages occur in the same vesicle released from the TGN.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Bond, S., Forgac, M. (2008). The Ras/cAMP/Protein Kinase A Pathway Regulates Glucose-dependent Assembly of the Vacuolar (H+)-ATPase in Yeast. J. Biol. Chem. 283: 36513-36521 [Abstract] [Full Text]
Moulin, P., Guiot, Y., Jonas, J.-C., Rahier, J., Devuyst, O., Henquin, J.-C. (2007). Identification and subcellular localization of the Na+/H+ exchanger and a novel related protein in the endocrine pancreas and adrenal medulla. J Mol Endocrinol 38: 409-422 [Abstract] [Full Text]
Kashemsant, N., Chan, C. B (2006). Impact of uncoupling protein-2 overexpression on proinsulin processing. J Mol Endocrinol 37: 517-526 [Abstract] [Full Text]
Sun-Wada, G.-H., Toyomura, T., Murata, Y., Yamamoto, A., Futai, M., Wada, Y. (2006). The a3 isoform of V-ATPase regulates insulin secretion from pancreatic {beta}-cells. J. Cell Sci. 119: 4531-4540 [Abstract] [Full Text]
Stiernet, P., Guiot, Y., Gilon, P., Henquin, J.-C. (2006). Glucose Acutely Decreases pH of Secretory Granules in Mouse Pancreatic Islets: MECHANISMS AND INFLUENCE ON INSULIN SECRETION. J. Biol. Chem. 281: 22142-22151 [Abstract] [Full Text]
Huang, K., Dong, J., Phillips, N. B., Carey, P. R., Weiss, M. A. (2005). Proinsulin Is Refractory to Protein Fibrillation: TOPOLOGICAL PROTECTION OF A PRECURSOR PROTEIN FROM CROSS-{beta} ASSEMBLY. J. Biol. Chem. 280: 42345-42355 [Abstract] [Full Text]
Halban, P. A., Irminger, J.-C. (2003). Mutant Proinsulin That Cannot Be Converted Is Secreted Efficiently from Primary Rat beta -Cells via the Regulated Pathway. Mol. Biol. Cell 14: 1195-1203 [Abstract] [Full Text]
Pothos, E. N, Mosharov, E., Liu, K.-P., Setlik, W., Haburcak, M., Baldini, G., Gershon, M. D, Tamir, H., Sulzer, D. (2002). Stimulation-dependent regulation of the pH, volume and quantal size of bovine and rodent secretory vesicles. J. Physiol. 542: 453-476 [Abstract] [Full Text]
Molinete, M., Dupuis, S., Brodsky, F. M., Halban, P. A. (2002). Role of clathrin in the regulated secretory pathway of pancreatic {beta}-cells. J. Cell Sci. 114: 3059-3066 [Abstract] [Full Text]
Hwang, S.-R., Steineckert, B., Yasothornsrikul, S., Sei, C. A., Toneff, T., Rattan, J., Hook, V. Y. H. (1999). Molecular Cloning of Endopin 1, a Novel Serpin Localized to Neurosecretory Vesicles of Chromaffin Cells. INHIBITION OF BASIC RESIDUE-CLEAVING PROTEASES BY ENDOPIN 1. J. Biol. Chem. 274: 34164-34173 [Abstract] [Full Text]
Hook, V. Y. H., Noctor, S., Sei, C. A., Toneff, T., Yasothornsrikul, S., Kang, Y.-H. (1999). Evidence for Functional Localization of the Proenkephalin-Processing Enzyme, Prohormone Thiol Protease, to Secretory Vesicles of Chromaffin Cells. Endocrinology 140: 3744-3754 [Abstract] [Full Text]
Urbe, S., Page, L. J., Tooze, S. A. (1998). Homotypic Fusion of Immature Secretory Granules during Maturation in a Cell-free Assay. JCB 143: 1831-1844 [Abstract] [Full Text]
Rindler, M. J. (1998). Carboxypeptidase E, a Peripheral Membrane Protein Implicated in the Targeting of Hormones to Secretory Granules, Co-aggregates with Granule Content Proteins at Acidic pH. J. Biol. Chem. 273: 31180-31185 [Abstract] [Full Text]
Teter, K., Chandy, G., Quinones, B., Pereyra, K., Machen, T., Moore, H.-P. H. (1998). Cellubrevin-targeted Fluorescence Uncovers Heterogeneity in the Recycling Endosomes. J. Biol. Chem. 273: 19625-19633 [Abstract] [Full Text]
Fernandez, C. J., Haugwitz, M., Eaton, B., Moore, H.-P. H. (1997). Distinct Molecular Events during Secretory Granule Biogenesis Revealed by Sensitivities to Brefeldin A. Mol. Biol. Cell 8: 2171-2185 [Abstract] [Full Text]
Kuliawat, R., Klumperman, J., Ludwig, T., Arvan, P. (1997). Differential Sorting of Lysosomal Enzymes Out of the Regulated Secretory Pathway in Pancreatic {beta}-Cells. JCB 137: 595-608 [Abstract] [Full Text]
Tanaka, S., Yora, T., Nakayama, K., Inoue, K., Kurosumi, K. (1997). Proteolytic Processing of Pro-opiomelanocortin Occurs in Acidifying Secretory Granules of AtT-20 Cells. J. Histochem. Cytochem. 45: 425-436 [Abstract] [Full Text]
Verchere, C. B., Paoletta, M., Neerman-Arbez, M., Rose, K., Irminger, J.-C., Gingerich, R. L., Kahn, S. E., Halban, P. A. (1996). Des-(, , , , )C-Peptide. A NOVEL SECRETORY PRODUCT OF THE RAT PANCREATIC BETA CELL PRODUCED BY TRUNCATION OF PROINSULIN CONNECTING PEPTIDE IN SECRETORY GRANULES. J. Biol. Chem. 271: 27475-27481 [Abstract] [Full Text]
Colomer, V., Kicska, G. A., Rindler, M. J. (1996). Secretory Granule Content Proteins and the Luminal Domains of Granule Membrane Proteins Aggregate in Vitro at Mildly Acidic pH. J. Biol. Chem. 271: 48-55 [Abstract] [Full Text]
Rothenberg, M. E., Eilertson, C. D., Klein, K., Zhou, Y., Lindberg, I., McDonald, J. K., Mackin, R. B., Noe, B. D. (1995). Processing of Mouse Proglucagon by Recombinant Prohormone Convertase 1 and Immunopurified Prohormone Convertase 2 in Vitro. J. Biol. Chem. 270: 10136-10146 [Abstract] [Full Text]
Sariola, M, Saraste, J, Kuismanen, E (1995). Communication of post-Golgi elements with early endocytic pathway: regulation of endoproteolytic cleavage of Semliki Forest virus p62 precursor. J. Cell Sci. 108: 2465-2475 [Abstract]
Wu, M. M., Grabe, M., Adams, S., Tsien, R. Y., Moore, H.-P. H., Machen, T. E. (2001). Mechanisms of pH Regulation in the Regulated Secretory Pathway. J. Biol. Chem. 276: 33027-33035 [Abstract] [Full Text]