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Altered cellular localisation and expression, together with unconventional protein trafficking, of prion protein, PrPC, in type 1 diabetes – published online 17/07/2021

Hiller graphical abstract

Helmut Hiller, Changjun Yang, Dawn E. Beachy, Irina Kusmartseva, Eduardo Candelario-Jalil, Amanda L. Posgai, Harry S. Nick, Desmond Schatz, Mark A. Atkinson, Clive H. Wasserfall

The expression of the non-neurodegenerative, normal isoform of cellular prion protein (PrPC) within pancreatic islets can affect glucose homeostasis in rodents. In this issue, Hiller et al ( evaluated PrPC expression and localisation in human pancreas samples from the Network for Pancreatic Organ donors with Diabetes. Compared with control tissues from individuals without diabetes, PRNP gene expression was reduced in pancreases from islet-autoantibody-positive donors but increased in pancreases from donors with type 1 diabetes. For all donor groups, PrPC localised specifically to the pancreatic islets. However, within pancreases from donors with type 1 diabetes, PrPC localised to beta cells of insulin-positive islets and alpha cells of insulin-negative islets. PrPC was detected in the endoplasmic reticulum and on the cell surface but not in the Golgi apparatus, suggesting unconventional trafficking in islet endocrine cells. PrPC co-localised with stress-inducible phosphoprotein 1 (STI1), which the authors suggest has potential implications for islet cell protection during type 1 diabetes pathogenesis. The authors conclude that these findings provide new insights into the role that PrPC may play in the pathogenesis of type 1 diabetes and speculate that intervention through PrPC protein–ligand interactions could be therapeutic in type 1 diabetes. However, they note that further studies are required.

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