title: Cellular prion protein localizes to the nucleus of endocrine and neuronal cells and interacts with structural chromatin components.
abstract: 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.
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. alexander.strom@ddz.uni-duesseldorf.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Wang
authors.forename: David J
authors.initials: DJ
authors.lastname: Picketts
authors.forename: Rudolph
authors.initials: R
authors.lastname: Reimer
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Stuke
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004703:Endocrine System / Q000166:cytology* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D034921:Lamin Type B / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D002843:Chromatin; D006657:Histones; D034921:Lamin Type B; D018621:PrPC Proteins