title: PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells.
abstract: The prion protein (PrP) plays a key role in prion disease pathogenesis. Although the misfolded and pathologic variant of this protein (PrP(SC)) has been studied in depth, the physiological role of PrP(C) remains elusive and controversial. PrP(C) is a cell-surface glycoprotein involved in multiple cellular functions at the plasma membrane, where it interacts with a myriad of partners and regulates several intracellular signal transduction cascades. However, little is known about the gene expression changes modulated by PrP(C) in animals and in cellular models. In this article, we present PrP(C)-dependent gene expression signature in N2a cells and its implication in the most overrepresented functions: cell cycle, cell growth and proliferation, and maintenance of cell shape. PrP(C) over-expression enhances cell proliferation and cell cycle re-entrance after serum stimulation, while PrP(C) silencing slows down cell cycle progression. In addition, MAP kinase and protein kinase B (AKT) pathway activation are under the regulation of PrP(C) in asynchronous cells and following mitogenic stimulation. These effects are due in part to the modulation of epidermal growth factor receptor (EGFR) by PrP(C) in the plasma membrane, where the two proteins interact in a multimeric complex. We also describe how PrP(C) over-expression modulates filopodia formation by Rho GTPase regulation mainly in an AKT-Cdc42-N-WASP-dependent pathway.
authors: Molecular and Cellular Neurobiotechnology Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Science Park, Barcelona, Spain; Department of Cell Biology, University of Barcelona (UB), Barcelona, Spain; Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Barcelona, Spain; Institute of Neuropathology, Bellvitge Biomedical Research Institute, Hospitalet de Llobregat, Spain.
authors: Franc
authors: F
authors: Llorens
authors: Patricia
authors: P
authors: Carulla
authors: Ana
authors: A
authors: Villa
authors: Juan M
authors: JM
authors: Torres
authors: Puri
authors: P
authors: Fortes
authors: Isidre
authors: I
authors: Ferrer
authors: José A
authors: JA
authors: del Río
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D021962:Membrane Microdomains / Q000502:physiology; D046228:Microarray Analysis; D008934:Mitogens / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D051058:Oncogene Protein v-akt / Q000502:physiology; D018621:PrPC Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D008934:Mitogens; D018621:PrPC Proteins; D034741:RNA, Small Interfering; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt
keywords: cell signaling; cellular prion protein; filopodia; gene expression; microarray; proliferation