Prion protein is essential for the RE1 silencing transcription factor (REST)-dependent developmental switch in synaptic NMDA receptors

Cell Death & Disease
Zhiqi SongDeming Zhao

Abstract

It is important that the correct amounts of GluN2 subunits are maintained, as they determine NMDAR functional properties, which are crucial to neuronal communication, synaptogenesis and cognitive function. The transcriptional repressor RE1 silencing transcription factor (REST) is critical for the postnatal developmental switch in NMDARs. However, the mechanisms triggering REST and the link between NMDARs and REST are unclear. Here we show a new physiological essential role for cellular prion protein (PrPC) in REST-dependent homeostasis and the developmental switch of NMDARs. REST and REST-associated proteins were overactivated in the hippocampi of Prnp knockout mice (Prnp 0/0 ) compared with wild-type Prnp (Prnp +/+ ) mice. This coincided with the disruption of the normal developmental switch from GluN2B-to-GluN2A in vivo. PrPC co-located with REST under physiological environments and mediated the translocation of REST in conditioners of NMDARs in vitro in Prnp +/+ hippocampal neurons. Regardless of whether REST was knocked down or overexpressed, deletion of PrPC not only disrupted REST-mediated distribution of mitochondria, but also prevented REST-regulated expression of GluN2B and GluN2A in Prnp 0/0 . Importantly, these effec...Continue Reading

References

Mar 14, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·E GillandH Hagberg
Dec 14, 2001·Proceedings of the National Academy of Sciences of the United States of America·J Ma, S Lindquist
May 2, 2002·The European Journal of Neuroscience·Nicole SalèsKenneth L Moya
Oct 3, 2003·British Medical Bulletin·C Weissmann, E Flechsig
Jan 18, 2005·Nature Reviews. Neuroscience·Jonathan M Levenson, J David Sweatt
Jul 19, 2005·Nature Neuroscience·Eric M SnyderPaul Greengard
Feb 13, 2007·Brain Research·Patrick TremblayStephen J DeArmond
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yitao LiuYu Tian Wang
Jun 16, 2007·Neuropharmacology·Jakob von EngelhardtHannah Monyer
Apr 30, 2008·The Journal of Cell Biology·Houman KhosravaniGerald W Zamponi
Dec 27, 2008·Neuron·Emiliana BorrelliPaolo Sassone-Corsi
Jul 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zhuo XuWei Lu
Jul 15, 2009·British Journal of Pharmacology·Laetitia MonyPierre Paoletti
Feb 11, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yasukazu TerasakiKazuo Kitagawa
Jul 14, 2010·Neuron·Ming-Chia LeeMichael D Ehlers
Aug 19, 2010·Pharmacological Reviews·Stephen F TraynelisRay Dingledine
Oct 5, 2010·Trends in Molecular Medicine·Claudio Soto, Nikunj Satani
Mar 15, 2011·The European Journal of Neuroscience·Pierre Paoletti
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shaomin LiDennis J Selkoe
Aug 9, 2011·Neurobiology of Aging·Fabrizio GardoniBarbara Picconi
Sep 11, 2012·Nature Neuroscience·Alma Rodenas-RuanoR Suzanne Zukin
May 21, 2013·Nature Reviews. Neuroscience·Pierre PaolettiQiang Zhou
Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Maria TalantovaStuart A Lipton
Mar 19, 2014·CNS Neuroscience & Therapeutics·Zhi-Qi SongDe-Ming Zhao
Mar 29, 2014·Nature·Tao LuBruce A Yankner
Apr 20, 2014·Neuron·Matthew P Parsons, Lynn A Raymond
Apr 25, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Naoki KanekoR Suzanne Zukin
Nov 5, 2014·Frontiers in Cell and Developmental Biology·Stefanie A G BlackShigeki Tsutsui
Dec 7, 2014·Journal of Molecular Neuroscience : MN·Zhiqi SongLifeng Yang
Dec 10, 2014·Antioxidants & Redox Signaling·Lisa GasperiniGiuseppe Legname

❮ Previous
Next ❯

Citations

Jan 8, 2020·International Journal of Molecular Sciences·Jose M Garcia-ManteigaJacopo Meldolesi

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
fluorescence microscopy
PCR
confocal microscopy

Software Mentioned

REST
SPSS
GraphPad Prism
Image J

Related Concepts

Related Feeds

Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is a form of of brain inflammation due to antibodies against NMDA receptors. Discover the latest research on anti-NMDA receptor encephalitis here.

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.