Cellular prion protein localizes to the nucleus of endocrine and neuronal cells and interacts with structural chromatin components

• Published in: European journal of cell biology Vol. 90; no. 5; pp. 414 - 419
• Main Authors: Strom, Alexander, Wang, Gen-Sheng, Picketts, David J., Reimer, Rudolph, Stuke, Andreas W., Scott, Fraser W.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.05.2011
• Subjects: Animals; Blood; blood glucose; Cell Line; Cell Nucleus - metabolism; chromatin; Chromatin - chemistry; Chromatin - metabolism; Endocrine System - cytology; Endocrine System - metabolism; fluorescent antibody technique; Histone H3; histones; Histones - metabolism; Islets; islets of Langerhans; Lamin B1; Lamin Type B - metabolism; Mice; Mice, Knockout; neurons; Neurons - cytology; Neurons - metabolism; Nucleus; prion diseases; Prion protein; prions; PrPC Proteins - genetics; PrPC Proteins - metabolism; Rats; tissues; transcription (genetics); Western blotting; β-cell; Nucleus; Lamin B1; Islets; β-cell; Prion protein; Histone H3
• ISSN: 0171-9335; 1618-1298; 1618-1298
• DOI: 10.1016/j.ejcb.2010.11.015

Several physiological processes have been purported for cellular prion protein (PrP C). However, the physiological function of PrP C is still unclear and the cellular localization of PrP C remains a subject of debate. PrP C is expressed in a wide range of tissues including islets of Langerhans. We previously demonstrated that the function of PrP C is associated with blood glucose regulation. Little is known of the function of PrP C in islet cells and specifically in β-cells. To get first insight into the putative role of PrP C in β-cells, we used far-Western immunoblotting and MS to identify candidate PrP C-interacting proteins. We also used Western blot, immunofluorescence (IF) and protein overlay IF to characterize the sub-cellular localization of PrP C. Here we demonstrate in vivo that PrP C is abundant in the nuclear lamina of endocrine and neuronal cells and interacts with histone H1 0, histone H3 and lamin B1. The interaction of PrP C with histone H3 suggests that it is involved in transcriptional regulation in the nucleus. This study reveals new avenues for the elucidation of the physiological function of PrP C in endocrine and neuronal cells as well as the molecular mechanisms leading to prion diseases.