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PMID:10806118
| Citation |
Arias, AE, Vélez-Granell, CS, Mayer, G and Bendayan, M (2000) Colocalization of chaperone Cpn60, proinsulin and convertase PC1 within immature secretory granules of insulin-secreting cells suggests a role for Cpn60 in insulin processing. J. Cell. Sci. 113 ( Pt 11):2075-83 |
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| Abstract |
Many of the mechanisms that control insulin processing and packaging by interaction with different elements along the secretory pathway remain poorly understood. We have investigated the possibility that Cpn60, a member of the heat shock protein family, may be present in rat insulin-secreting cells, participating in the proinsulin-insulin maturation process. Immunofluorescence and high resolution immunocytochemical studies revealed the presence of the Cpn60 protein all along the insulin secretory pathway, being particularly abundant over the proinsulin-containing immature secretory granules. Double-labeling experiments showed associations between Cpn60 and proinsulin, as well as between Cpn60 and PC1 convertase, with a preferential binding to proinsulin. These findings paralleled those of coimmunoprecipitation studies showing the Cpn60 chaperone and the mature form of the PC1 convertase in proinsulin immunoprecipitates, as well as the PC1 in Cpn60 immunoprecipitates from total islet cell extracts. In vitro binding of Cpn60 to proinsulin, insulin and glucagon was also documented. Cpn60, significantly abundant in proinsulin-containing secretory granules where conversion of proinsulin to insulin takes place, and the colocalization of the chaperone with proinsulin and PC1 convertase suggest that the Cpn60 protein may play a role directing precise molecular interactions during insulin processing and/or packaging. |
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| Keywords |
Animals; Aspartic Acid Endopeptidases/metabolism; Chaperonin 60/metabolism; Cytoplasmic Granules/enzymology; Cytoplasmic Granules/metabolism; Insulin/metabolism; Islets of Langerhans/enzymology; Islets of Langerhans/metabolism; Islets of Langerhans/ultrastructure; Microscopy, Electron; Proinsulin/metabolism; Proprotein Convertases; Protein Binding; Rats; Rats, Sprague-Dawley |
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