Anti-GRIN3B Antibody (ARG65277)

Total Page:16

File Type:pdf, Size:1020Kb

Anti-GRIN3B Antibody (ARG65277) Product datasheet [email protected] ARG65277 Package: 100 μg anti-GRIN3B antibody Store at: -20°C Summary Product Description Goat Polyclonal antibody recognizes GRIN3B Tested Reactivity Hu Tested Application WB Host Goat Clonality Polyclonal Isotype IgG Target Name GRIN3B Antigen Species Human Immunogen C-EAPPHSGRPGSQ Conjugation Un-conjugated Alternate Names NMDAR3B; GluN3B; N-methyl-D-aspartate receptor subtype 3B; Glutamate receptor ionotropic, NMDA 3B; NR3B Application Instructions Application table Application Dilution WB 0.5 - 1.5 µg/ml Application Note WB: Recommend incubate at RT for 1h. * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Calculated Mw 113 kDa Properties Form Liquid Purification Purified from goat serum by ammonium sulphate precipitation followed by antigen affinity chromatography using the immunizing peptide. Buffer Tris saline (pH 7.3), 0.02% Sodium azide and 0.5% BSA Preservative 0.02% Sodium azide Stabilizer 0.5% BSA Concentration 0.5 mg/ml Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C or below. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. www.arigobio.com 1/2 Note For laboratory research only, not for drug, diagnostic or other use. Bioinformation Database links GeneID: 116444 Human Swiss-port # O60391 Human Gene Symbol GRIN3B Gene Full Name glutamate receptor, ionotropic, N-methyl-D-aspartate 3B Function NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. [UniProt] Research Area Neuroscience antibody Images ARG65277 anti-GRIN3B antibody WB image Western Blot: Human Cerebellum lysate (35 µg protein in RIPA buffer) stained with ARG65277 anti-GRIN3B antibody at 0.5 µg/ml dilution. www.arigobio.com 2/2 Powered by TCPDF (www.tcpdf.org).
Recommended publications
  • Original Article Upregulation of HOXA13 As a Potential Tumorigenesis and Progression Promoter of LUSC Based on Qrt-PCR and Bioinformatics
    Int J Clin Exp Pathol 2017;10(10):10650-10665 www.ijcep.com /ISSN:1936-2625/IJCEP0065149 Original Article Upregulation of HOXA13 as a potential tumorigenesis and progression promoter of LUSC based on qRT-PCR and bioinformatics Rui Zhang1*, Yun Deng1*, Yu Zhang1, Gao-Qiang Zhai1, Rong-Quan He2, Xiao-Hua Hu2, Dan-Ming Wei1, Zhen-Bo Feng1, Gang Chen1 Departments of 1Pathology, 2Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China. *Equal contributors. Received September 7, 2017; Accepted September 29, 2017; Epub October 1, 2017; Published October 15, 2017 Abstract: In this study, we investigated the levels of homeobox A13 (HOXA13) and the mechanisms underlying the co-expressed genes of HOXA13 in lung squamous cancer (LUSC), the signaling pathways in which the co-ex- pressed genes of HOXA13 are involved and their functional roles in LUSC. The clinical significance of 23 paired LUSC tissues and adjacent non-tumor tissues were gathered. HOXA13 levels in LUSC were detected by quantita- tive real-time polymerase chain reaction (qRT-PCR). HOXA13 levels in LUSC from The Cancer Genome Atlas (TCGA) and Oncomine were analyzed. We performed receiver operator characteristic (ROC) curves of various clinicopath- ological features of LUSC. Co-expressed of HOXA13 were collected from MEM, cBioPortal and GEPIA. The func- tions and pathways of the most reliable overlapped genes were achieved from the Gene Otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. The protein-protein interaction (PPI) net- works were mapped using STRING. HOXA13 in LUSC were markedly upregulated compared with those in the non- cancerous controls as demonstrated by qRT-PCR (LUSC: 0.330±0.360; CONTROLS: 0.155±0.142; P=0.021).
    [Show full text]
  • 1 Evidence for Gliadin Antibodies As Causative Agents in Schizophrenia
    1 Evidence for gliadin antibodies as causative agents in schizophrenia. C.J.Carter PolygenicPathways, 20 Upper Maze Hill, Saint-Leonard’s on Sea, East Sussex, TN37 0LG [email protected] Tel: 0044 (0)1424 422201 I have no fax Abstract Antibodies to gliadin, a component of gluten, have frequently been reported in schizophrenia patients, and in some cases remission has been noted following the instigation of a gluten free diet. Gliadin is a highly immunogenic protein, and B cell epitopes along its entire immunogenic length are homologous to the products of numerous proteins relevant to schizophrenia (p = 0.012 to 3e-25). These include members of the DISC1 interactome, of glutamate, dopamine and neuregulin signalling networks, and of pathways involved in plasticity, dendritic growth or myelination. Antibodies to gliadin are likely to cross react with these key proteins, as has already been observed with synapsin 1 and calreticulin. Gliadin may thus be a causative agent in schizophrenia, under certain genetic and immunological conditions, producing its effects via antibody mediated knockdown of multiple proteins relevant to the disease process. Because of such homology, an autoimmune response may be sustained by the human antigens that resemble gliadin itself, a scenario supported by many reports of immune activation both in the brain and in lymphocytes in schizophrenia. Gluten free diets and removal of such antibodies may be of therapeutic benefit in certain cases of schizophrenia. 2 Introduction A number of studies from China, Norway, and the USA have reported the presence of gliadin antibodies in schizophrenia 1-5. Gliadin is a component of gluten, intolerance to which is implicated in coeliac disease 6.
    [Show full text]
  • NMDA Receptor Dynamics Dictate Neuronal Plasticity and Function
    NMDA Receptor Dynamics Dictate Neuronal Plasticity and Function Tommy Weiss Sadan, Ph.D. and Melanie R. Grably, Ph.D. N-Methyl-D-Aspartate Receptor (NMDAR) are ubiquitously expressed along the central nervous system and are instrumental to various physiological processes such as synaptic plasticity and learning. Nevertheless, several mental disabilities including schizophrenia and Alzheimer’s disease are all related to NMDAR dysfunction. Here, we review many aspects of NMDAR function and regulation and describe their involvement in pathophysiological states using Alomone Labs products. Right: Cell surface detection of GluN2B in rat hippocampal neurons. Introduction Mechanism of Action Glutamate is a key neuro-transmitter in the central nervous system and NMDAR activation depends on sequential conformational changes to acts on a variety of cell surface receptors, collectively termed ionotropic relieve the magnesium blockade which is achieved by rapid membrane glutamate receptors (iGluRs)15. The N-Methyl-D-Aspartate receptors (NMDAR) depolarization and binding of both glycine and glutamate ligands6, 21. This in are members of the iGluR superfamily and are pivotal to many physiological turn removes the inhibitory electrostatic forces of magnesium and enables processes such as the formation of long term memory, synaptic plasticity calcium influx and transmission of long lasting signals (i.e. long-term and many other cognitive functions. Therefore, it is not surprising that potentiation), a key mechanism to learning and memory formation10.
    [Show full text]
  • Gene Expression Studies in Depression Development and Treatment
    Mariani et al. Translational Psychiatry (2021) 11:354 https://doi.org/10.1038/s41398-021-01469-6 Translational Psychiatry REVIEW ARTICLE Open Access Gene expression studies in Depression development and treatment: an overview of the underlying molecular mechanisms and biological processes to identify biomarkers Nicole Mariani 1, Nadia Cattane2,CarminePariante 1 and Annamaria Cattaneo 2,3 Abstract A combination of different risk factors, such as genetic, environmental and psychological factors, together with immune system, stress response, brain neuroplasticity and the regulation of neurotransmitters, is thought to lead to the development of major depressive disorder (MDD). A growing number of studies have tried to investigate the underlying mechanisms of MDD by analysing the expression levels of genes involved in such biological processes. These studies have shown that MDD is not just a brain disorder, but also a body disorder, and this is mainly due to the interplay between the periphery and the Central Nervous System (CNS). To this purpose, most of the studies conducted so far have mainly dedicated to the analysis of the gene expression levels using postmortem brain tissue as well as peripheral blood samples of MDD patients. In this paper, we reviewed the current literature on candidate gene expression alterations and the few existing transcriptomics studies in MDD focusing on inflammation, neuroplasticity, neurotransmitters and stress-related genes. Moreover, we focused our attention on studies, which have investigated 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; mRNA levels as biomarkers to predict therapy outcomes. This is important as many patients do not respond to antidepressant medication or could experience adverse side effects, leading to the interruption of treatment.
    [Show full text]
  • GRIN3B Antibody Cat
    GRIN3B Antibody Cat. No.: 56-326 GRIN3B Antibody GRIN3B Antibody immunohistochemistry analysis in formalin fixed and paraffin embedded human brain tissue followed by peroxidase conjugation of the secondary antibody and DAB staining. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This GRIN3B antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 904-933 amino acids from the C-terminal region of human GRIN3B. TESTED APPLICATIONS: IHC-P, WB For WB starting dilution is: 1:1000 APPLICATIONS: For IHC-P starting dilution is: 1:10~50 PREDICTED MOLECULAR 113 kDa WEIGHT: September 23, 2021 1 https://www.prosci-inc.com/grin3b-antibody-56-326.html Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: GRIN3B Glutamate receptor ionotropic, NMDA 3B, GluN3B, N-methyl-D-aspartate receptor ALTERNATE NAMES: subtype 3B, NMDAR3B, NR3B, GRIN3B ACCESSION NO.: O60391 GENE ID: 116444 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References GRIN3B is a NMDA receptor subtype of glutamate-gated ion channels with reduced single- BACKGROUND: channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium.
    [Show full text]
  • Research Article Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed Hipscs To
    Hindawi Publishing Corporation Stem Cells International Volume 2013, Article ID 784629, 25 pages http://dx.doi.org/10.1155/2013/784629 Research Article Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny Leonhard Linta,1 Marianne Stockmann,1 Qiong Lin,2 André Lechel,3 Christian Proepper,1 Tobias M. Boeckers,1 Alexander Kleger,3 and Stefan Liebau1 1 InstituteforAnatomyCellBiology,UlmUniversity,Albert-EinsteinAllee11,89081Ulm,Germany 2 Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen, Pauwelstrasse 30, 52074 Aachen, Germany 3 Department of Internal Medicine I, Ulm University, Albert-Einstein Allee 11, 89081 Ulm, Germany Correspondence should be addressed to Alexander Kleger; [email protected] and Stefan Liebau; [email protected] Received 31 January 2013; Accepted 6 March 2013 Academic Editor: Michael Levin Copyright © 2013 Leonhard Linta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated.
    [Show full text]
  • Stem Cells and Ion Channels
    Stem Cells International Stem Cells and Ion Channels Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Stem Cells and Ion Channels Stem Cells International Stem Cells and Ion Channels Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Copyright © 2013 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Stem Cells International.” All articles are open access articles distributed under the Creative Com- mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Nadire N. Ali, UK Joseph Itskovitz-Eldor, Israel Pranela Rameshwar, USA Anthony Atala, USA Pavla Jendelova, Czech Republic Hannele T. Ruohola-Baker, USA Nissim Benvenisty, Israel Arne Jensen, Germany D. S. Sakaguchi, USA Kenneth Boheler, USA Sue Kimber, UK Paul R. Sanberg, USA Dominique Bonnet, UK Mark D. Kirk, USA Paul T. Sharpe, UK B. Bunnell, USA Gary E. Lyons, USA Ashok Shetty, USA Kevin D. Bunting, USA Athanasios Mantalaris, UK Igor Slukvin, USA Richard K. Burt, USA Pilar Martin-Duque, Spain Ann Steele, USA Gerald A. Colvin, USA EvaMezey,USA Alexander Storch, Germany Stephen Dalton, USA Karim Nayernia, UK Marc Turner, UK Leonard M. Eisenberg, USA K. Sue O’Shea, USA Su-Chun Zhang, USA Marina Emborg, USA J. Parent, USA Weian Zhao, USA Josef Fulka, Czech Republic Bruno Peault, USA Joel C. Glover, Norway Stefan Przyborski, UK Contents Stem Cells and Ion Channels, Stefan Liebau,
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • Ligand-Gated Ion Channels
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: Ligand-gated ion channels. British Journal of Pharmacology (2015) 172, 5870–5903 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Ligand-gated ion channels Stephen PH Alexander1, John A Peters2, Eamonn Kelly3, Neil Marrion3, Helen E Benson4, Elena Faccenda4, Adam J Pawson4, Joanna L Sharman4, Christopher Southan4, Jamie A Davies4 and CGTP Collaborators L 1 School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, N 2Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/ doi/10.1111/bph.13350/full. Ligand-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage- gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets.
    [Show full text]
  • Retrograde Inhibition by a Specific Subset of Interpeduncular Α5 Nicotinic Neurons Regulates Nicotine Preference
    Retrograde inhibition by a specific subset of interpeduncular α5 nicotinic neurons regulates nicotine preference Jessica L. Ablesa,b,c, Andreas Görlicha,1, Beatriz Antolin-Fontesa,2,CuidongWanga, Sylvia M. Lipforda, Michael H. Riada, Jing Rend,e,3,FeiHud,e,4,MinminLuod,e,PaulJ.Kennyc, Nathaniel Heintza,f,5, and Ines Ibañez-Tallona,5 aLaboratory of Molecular Biology, The Rockefeller University, New York, NY 10065; bDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029; cDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029; dNational Institute of Biological Sciences, Beijing 102206, China; eSchool of Life Sciences, Tsinghua University, Beijing 100084, China; and fHoward Hughes Medical Institute, The Rockefeller University, New York, NY 10065 Contributed by Nathaniel Heintz, October 23, 2017 (sent for review October 5, 2017; reviewed by Jean-Pierre Changeux and Lorna W. Role) Repeated exposure to drugs of abuse can produce adaptive changes nicotine withdrawal, and optical activation of IPN GABAergic cells that lead to the establishment of dependence. It has been shown that is sufficient to produce a withdrawal syndrome, while blockade of allelic variation in the α5 nicotinic acetylcholine receptor (nAChR) gene GABAergic cells in the IPN reduced symptoms of withdrawal (17). CHRNA5 is associated with higher risk of tobacco dependence. In the Taken together these studies highlight the critical role of α5in brain, α5-containing nAChRs are expressed at very high levels in the regulating behavioral responses to nicotine. Here we characterize two subpopulations of GABAergic interpeduncular nucleus (IPN). Here we identified two nonoverlapping Amigo1 Epyc α + α Amigo1 α Epyc neurons in the IPN that express α5: α5- and α5- neu- 5 cell populations ( 5- and 5- ) in mouse IPN that respond α Amigo1 α Epyc differentially to nicotine.
    [Show full text]
  • The Identification and Functional Implications of Human-Specific
    BMC Evolutionary Biology BioMed Central Research article Open Access The identification and functional implications of human- specific "fixed" amino acid substitutions in the glutamate receptor family Hiroki Goto1, Kazunori Watanabe1, Naozumi Araragi1, Rui Kageyama1, Kunika Tanaka1, Yoko Kuroki3, Atsushi Toyoda4, Masahira Hattori5, Yoshiyuki Sakaki2, Asao Fujiyama2,6, Yasuyuki Fukumaki*1 and Hiroki Shibata1 Address: 1Division of Human Moelcular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan, 2RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan, 3RIKEN Advanced Science Institute (ASI), Advanced Computational Sciences Department, Computational Systems Biology Research Group, Synthetic Biology Team, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama, Kanagawa, Japan, 4Comparative Genomics Laboratory, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan, 5Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan and 6National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo, 101-8430, Japan Email: Hiroki Goto - [email protected]; Kazunori Watanabe - [email protected]; Naozumi Araragi - naozumi.araragi@uni- wuerzburg.de; Rui Kageyama - [email protected]; Kunika Tanaka - [email protected]; Yoko Kuroki - [email protected]; Atsushi Toyoda - [email protected]; Masahira Hattori - [email protected]; Yoshiyuki Sakaki - [email protected]; Asao Fujiyama - [email protected]; Yasuyuki Fukumaki* - [email protected]; Hiroki Shibata - [email protected] * Corresponding author Published: 8 September 2009 Received: 14 November 2008 Accepted: 8 September 2009 BMC Evolutionary Biology 2009, 9:224 doi:10.1186/1471-2148-9-224 This article is available from: http://www.biomedcentral.com/1471-2148/9/224 © 2009 Goto et al; licensee BioMed Central Ltd.
    [Show full text]
  • The Pathogenic S688Y Mutation in the Ligand-Binding Domain Of
    www.nature.com/scientificreports OPEN The pathogenic S688Y mutation in the ligand‑binding domain of the GluN1 subunit regulates the properties of NMDA receptors Kristyna Skrenkova1,6, Jae‑man Song2,6, Stepan Kortus1,6, Marharyta Kolcheva1,3, Jakub Netolicky1,3, Katarina Hemelikova1, Martina Kaniakova1, Barbora Hrcka Krausova1, Tomas Kucera4, Jan Korabecny4,5, Young Ho Suh2* & Martin Horak1* Although numerous pathogenic mutations have been identifed in various subunits of N‑methyl‑D‑ aspartate receptors (NMDARs), ionotropic glutamate receptors that are central to glutamatergic neurotransmission, the functional efects of these mutations are often unknown. Here, we combined in silico modelling with microscopy, biochemistry, and electrophysiology in cultured HEK293 cells and hippocampal neurons to examine how the pathogenic missense mutation S688Y in the GluN1 NMDAR subunit afects receptor function and trafcking. We found that the S688Y mutation signifcantly increases the EC50 of both glycine and d‑serine in GluN1/GluN2A and GluN1/GluN2B receptors, and signifcantly slows desensitisation of GluN1/GluN3A receptors. Moreover, the S688Y mutation reduces the surface expression of GluN3A‑containing NMDARs in cultured hippocampal neurons, but does not afect the trafcking of GluN2‑containing receptors. Finally, we found that the S688Y mutation reduces Ca2+ infux through NMDARs and reduces NMDA‑induced excitotoxicity in cultured hippocampal neurons. These fndings provide key insights into the molecular mechanisms that underlie the regulation of NMDAR subtypes containing pathogenic mutations. N-methyl-D-aspartate receptors (NMDARs) are a subclass of ionotropic glutamate receptors that play an essential role in mediating excitatory neurotransmission and synaptic plasticity in the mammalian central nervous system (CNS)1–3. NMDARs are tetramers comprised of two GluN1 subunits (with eight splice variants) together with two GluN2 (GluN2A through GluN2D) and/or two GluN3 (GluN3A and GluN3B) subunits3,4.
    [Show full text]