Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons

The Journal of Physiology
Anton IvanovIgor Medina

Abstract

The extracellular signal-regulated kinases (ERK) signalling cascade is a key pathway that mediates the NMDA receptor (NMDAR)-dependent neuronal plasticity and survival. However, it is not clear yet how NMDARs regulate ERK activity. Stimulation of the NMDARs induces a complex modification of ERK that includes both ERK activation and inactivation and depends on particular experimental conditions. Here we show that there exists a differential restriction in the regulation of ERK activity that depends on the pool of NMDAR that was activated. The synaptic pool of NMDARs activates ERK whereas the extrasynaptic pool does not; on the contrary, it triggers a signalling pathway that results in the inactivation of ERK. As a result, simultaneous activation of both extrasynaptic and synaptic NMDAR using bath application of NMDA or glutamate (a typical protocol explored in the majority of studies) produced ERK activation that depended on the concentration of agonists and was always significantly weaker than those mediated by synaptic NMDARs. Since the activation of the extrasynaptic NMDA is attributed mainly to global release of glutamate occurring at pathological conditions including hypoxic/ischaemic insults, traumas and epileptic brain da...Continue Reading

References

Oct 3, 1999·Physiological Reviews·P Lipton
Jun 12, 2001·Current Opinion in Neurobiology·S Cull-CandyM Farrant
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·J Paige Adams, J David Sweatt
Jan 22, 2003·Trends in Neurosciences·Giles E Hardingham, Hilmar Bading
Jun 26, 2003·The European Journal of Neuroscience·Miri Goldin, Menahem Segal
Feb 21, 2004·Nature Reviews. Neuroscience·Gareth M Thomas, Richard L Huganir
Mar 31, 2004·Cellular and Molecular Life Sciences : CMLS·M Arundine, M Tymianski
May 18, 2004·The Journal of Physiology·Natasha A LozovayaOleg A Krishtal
May 21, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Annalisa ScimemiDmitri A Rusakov
Sep 10, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Peter V MasseyZafar I Bashir
Jul 22, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sven BerberichGeorg Köhr
Jul 29, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Meilan ZhaoSerena M Dudek
Sep 16, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carl WeitlaufDanny G Winder
Dec 2, 2005·Journal of Neurophysiology·Christopher G ThomasGary L Westbrook

❮ Previous
Next ❯

Citations

May 12, 2012·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Mark BandAaron Avivi
Jul 25, 2006·Cell and Tissue Research·Georg Köhr
Dec 17, 2010·Journal of Bioenergetics and Biomembranes·Florence Molinari
Oct 6, 2007·Molecular Neurobiology·Evgeni PonimaskinAlexander Dityatev
May 24, 2011·Molecular Neurobiology·Frank Fetterolf, Kelly A Foster
Aug 27, 2013·Neuropharmacology·Sandra I MotaA Cristina Rego
Nov 4, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Adam J FunkJames H Meador-Woodruff
Apr 22, 2008·Nature Reviews. Drug Discovery·Gerard SanacoraHusseini K Manji
Sep 16, 2010·Nature Reviews. Neuroscience·Giles E Hardingham, Hilmar Bading
Dec 1, 2011·Nature Reviews. Neuroscience·Maurizio PopoliGerard Sanacora
Jul 20, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Gang LeiKenneth M Johnson
Dec 25, 2008·The Journal of Biological Chemistry·Michael A BeazelyJohn F Macdonald
Oct 11, 2008·The Journal of Biological Chemistry·Joseph S TauskelaGeoffrey A R Mealing
Nov 6, 2013·The Journal of Cell Biology·Hailong HouHouhui Xia
Jun 2, 2012·TheScientificWorldJournal·Ronald S Petralia
Jul 28, 2011·Cold Spring Harbor Perspectives in Biology·Anna M Hagenston, Hilmar Bading
Jun 2, 2012·International Journal of Alzheimer's Disease·Tetsuya Mizuno
Nov 15, 2007·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Sofia Papadia, Giles E Hardingham
May 9, 2006·Genome Biology·Bryen A Jordan, Edward B Ziff
Feb 29, 2008·PLoS Biology·Daniela C DieterichMichael R Kreutz
Nov 1, 2008·PLoS Computational Biology·David M Santucci, Sridhar Raghavachari
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shaomin LiDennis J Selkoe
May 13, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eduardo F Gallo, Costantino Iadecola
Aug 5, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Deborah K VergesJohn R Cirrito
Jan 18, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Megan L BradyKevin K Caldwell
Jun 10, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Can GaoJelena Radulovic
Jul 25, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jian XuPaul J Lombroso
Jun 3, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ana SaavedraEsther Pérez-Navarro
Nov 11, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Holly J CarlisleMary B Kennedy
May 11, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Christine M WrogeSteven Mennerick
May 21, 2011·Journal of the American Society of Nephrology : JASN·Milica BozicJosé M Valdivielso
Mar 30, 2013·Brain Structure & Function·Marina MikhaylovaMichael R Kreutz
Sep 24, 2013·Neurobiology of Learning and Memory·Katherine LeaderbrandJelena Radulovic
Jan 22, 2014·Molecular Neurobiology·Pavel I Ortinski

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.