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Cytosolic Aggregation of Cellular Prion Protein Confined to Pancreatic Beta‐Cells
Author(s) -
Strom Alexander,
Wang GenSheng,
Reimer Rudolph,
Finegood Diane T,
Scott Fraser W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1134-a
Subject(s) - cytosol , nod mice , pancreas , biology , enteroendocrine cell , microbiology and biotechnology , islet , endocrinology , medicine , chemistry , diabetes mellitus , hormone , biochemistry , endocrine system , enzyme
Cellular prion protein (PrPC) is expressed in several tissues including neurons and pancreatic islets. To investigate whether PrPC expression was altered during the development of diabetes, we examined the pancreas in diabetes‐prone BioBreeding (BBdp) rats as well as non‐obese diabetic mice using light, fluorescent and confocal microscopy. PrPC was abundantly expressed in the four major endocrine cells within islets in BBdp rats and NOD mice. Surprisingly, cytosolic PrPC inclusions were observed in a subpopulation of beta‐cells in rats only. Inclusions were present in the islets of several rat strains including Wistar Furth, Sprague Dawley and Komeda. PrPC expression in the cytosol was weak, with strong staining of the cell membrane and pronounced aggregation in a subset of rat beta‐cells, particularly in older BBdp animals. The frequency of beta‐cells with inclusions increased with age in BBdp but not in controls. Moreover, in Sprague Dawley rats chronically infused with glucose, cytosolic PrPC expression was suppressed whereas the number of beta‐cells with inclusions increased. There was no co‐localization of gamma‐tubulin (microtubule complex), ubiquitin and proteasomes (protein degradation) and HSP70 (protein folding) with the PrPC inclusions consistent with proper folding of the PrPC protein. Thus, PrPC could play a role in glucoregulation and/or diabetes pathogenesis. (Supported by CIHR, CDA and JDRF) AS and GSW contributed equally.