title: Involvement of molecular chaperones in the aberrant aggregation of secretory proteins in pancreatic acinar cells.
abstract: Molecular chaperones have recently been shown to be accurately located along distinct cellular compartments of the secretory pathway of pancreatic acinar cells. Since the aberrant aggregation of secretory proteins leading to the formation of RER intracisternal crystals induced by DL-p-chlorophenylalanine methyl ester (CPME) comprises major changes in the sorting, selective transport, and/or posttranslational modifications of secretory proteins, we decided to investigate the possible involvement of chaperones in this phenomenon by applying the protein A-gold immunocytochemical approach. In addition to their presence in the cellular compartments of the secretory pathway, the chaperonins cpn10 and cpn60 were found to also be concentrated in the RER intracisternal crystals. In contrast, the hsp70 protein remained confined to the trans-Golgi network and was absent from the crystals. In both control and experimental conditions the three chaperones were present in mitochondria. Quantitative evaluations confirmed these observations and revealed an overall decrease in the labeling, particularly for hsp70 after CPME treatment. These labeling patterns suggest a participation of the chaperonins cpn10 and cpn60 but not of the hsp70 in the aberrant aggregation of secretory proteins leading to RER crystal formation. The role played by chaperones in this process, however, remains to be elucidated.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Université de Montréal, Quebec, Canada.
authors.forename: A E
authors.initials: AE
authors.lastname: Arias
authors.forename: C S
authors.initials: CS
authors.lastname: Vélez-Granell
authors.forename: J A
authors.initials: JA
authors.lastname: Torres-Ruíz
authors.forename: M
authors.initials: M
authors.lastname: Bendayan
mesh_terms: D000681:Amylases / Q000032:analysis / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D018835:Chaperonin 10 / Q000032:analysis / Q000378:metabolism; D018834:Chaperonin 60 / Q000032:analysis / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000502:physiology / Q000648:ultrastructure; D010134:Fenclonine / Q000031:analogs & derivatives / Q000494:pharmacology; D006056:Golgi Apparatus / Q000502:physiology / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000032:analysis / Q000378:metabolism*; D015388:Organelles / Q000502:physiology* / Q000648:ultrastructure; D010179:Pancreas / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D018832:Molecular Chaperones; C020261:4-chlorophenylalanine methyl ester; D000681:Amylases; D010134:Fenclonine