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

Several physiological processes have been purported for cellular prion protein (PrPC). However, the physiological function of PrPC is still unclear and the cellular localization of PrPC remains a subject of debate. PrPC is expressed in a wide range of tissues including islets of Langerhans. We previously demonstrated that the function of PrPC is associated with blood glucose regulation. Little is known of the function of PrPC in islet cells and specifically in β-cells. To get first insight into the putative role of PrPC in β-cells, we used far-Western immunoblotting and MS to identify candidate PrPC-interacting proteins. We also used Western blot, immunofluorescence (IF) and protein overlay IF to characterize the sub-cellular localization of PrPC. Here we demonstrate in vivo that PrPC is abundant in the nuclear lamina of endocrine and neuronal cells and interacts with histone H10, histone H3 and lamin B1. The interaction of PrPC 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 PrPC in endocrine and neuronal cells as well as the molecular mechanisms leading to prion diseases.