Proteoglycans support proper granule formation in pancreatic acinar cells.

Zymogen granules (ZG) are specialized organelles in the exocrine pancreas which allow digestive enzyme storage and regulated secretion. The molecular mechanisms of their biogenesis and the sorting of zymogens are still incompletely understood. Here, we investigated the role of proteoglycans in granu...

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Publicado en:Histochemistry & Cell Biology Vol. 144; no. 4; pp. 331 - 347
Autores principales: Aroso, Miguel, Agricola, Brigitte, Hacker, Christian, Schrader, Michael
Formato: Journal Article
Publicado: Springer Nature Oct2015
Acceso en línea:Ver este registro en EBSCOhost
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        atl: Proteoglycans support proper granule formation in pancreatic acinar cells.
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          Aroso, Miguel
          Agricola, Brigitte
          Hacker, Christian
          Schrader, Michael
        affil: Centre for Cell Biology and Department of Biology, University of Aveiro, Campus Universitário de Santiago 3810-193 Aveiro Portugal
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      ab: Zymogen granules (ZG) are specialized organelles in the exocrine pancreas which allow digestive enzyme storage and regulated secretion. The molecular mechanisms of their biogenesis and the sorting of zymogens are still incompletely understood. Here, we investigated the role of proteoglycans in granule formation and secretion of zymogens in pancreatic AR42J cells, an acinar model system. Cupromeronic Blue cytochemistry and biochemical studies revealed an association of proteoglycans primarily with the granule membrane. Removal of proteoglycans by carbonate treatment led to a loss of membrane curvature indicating a supportive role in the maintenance of membrane shape and stability. Chemical inhibition of proteoglycan synthesis impaired the formation of normal electron-dense granules in AR42J cells and resulted in the formation of unusually small granule structures. These structures still contained the zymogen carboxypeptidase, a cargo molecule of secretory granules, but migrated to lighter fractions after density gradient centrifugation. Furthermore, the basal secretion of amylase was increased in AR42J cells after inhibitor treatment. In addition, irregular-shaped granules appeared in pancreatic lobules. We conclude that the assembly of a proteoglycan scaffold at the ZG membrane is supporting efficient packaging of zymogens and the proper formation of stimulus-competent storage granules in acinar cells of the pancreas.
      pubtype: Academic Journal
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    language: English
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