CREB-dependent gene regulation by prion protein: impact on MMP-9 and beta-dystroglycan

Cellular Signalling
Elodie PradinesSophie Mouillet-Richard

Abstract

Corruption of the normal function of the cellular prion protein (PrP(C)) by the scrapie isoform (PrP(Sc)) emerges as a critical causal event in Transmissible Spongiform Encaphalopathies (TSE) pathogenesis. However, PrP(C) physiological role remains unclear. By exploiting the properties of the 1C11 neuroectodermal cell line, able to convert into 1C11(5-HT) serotonergic or 1C11(NE) noradrenergic neuronal cells, we assigned a signaling function to PrP(C). Here, we establish that antibody-mediated PrP(C) ligation promotes the recruitment of the cAMP responsive element binding protein (CREB) transcription factor downstream from the MAPK ERK1/2, in 1C11 precursor cells and their 1C11(5-HT) and 1C11(NE) neuronal progenies. Whatever the differentiation state of 1C11 cells, the PrP(C)-dependent CREB activation triggers Egr-1 and c-fos transcription, two immediate early genes that relay CREB's role in cell survival and proliferation as well as in neuronal plasticity. Furthermore, in 1C11-derived neuronal cells, we draw a link between the PrP(C)-CREB coupling and a transcriptional regulation of the metalloproteinase MMP-9 and its inhibitor TIMP-1, which play pivotal roles in neuronal pathophysiology. Finally, the PrP(C)-dependent control ...Continue Reading

References

Mar 17, 2000·Brain Research. Molecular Brain Research·E GranerR R Brentani
Mar 29, 2000·The Journal of Biological Chemistry·S Mouillet-RichardO Kellermann
Sep 16, 2000·Science·S Mouillet-RichardO Kellermann
Dec 8, 2004·Cellular and Molecular Life Sciences : CMLS·B HugelJ-M Freyssinet
Apr 27, 2005·The Journal of Cell Biology·Antonella SantuccioneMelitta Schachner
May 6, 2006·Neuron·David A Harris, Heather L True

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Citations

Jan 11, 2013·Cell Death & Disease·E PradinesS Mouillet-Richard
Sep 22, 2015·Frontiers in Immunology·Maren K BakkebøMichael A Tranulis
Mar 23, 2012·Prion·Franc Llorens, José Antonio Del Río
Nov 5, 2014·Frontiers in Cell and Developmental Biology·Xavier Roucou
May 9, 2014·Scientific Reports·Julia Hernandez-RappSophie Mouillet-Richard
Oct 16, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·H I YooS H Kim
Sep 25, 2019·International Journal of Molecular Sciences·Agnese De MarioMaria Catia Sorgato

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