DOCSLIB.ORG

Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated K+ Channel Integrity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated K+ Channel Integrity Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated K + Channel Integrity This information is current as Xuejiao Dong, Lisi Wei, Xueheng Guo, Zhiyong Yang, of September 24, 2021. Chuan Wu, Peiyu Li, Lu Lu, Hai Qi, Yan Shi, Xiaoyu Hu, Li Wu, Liangyi Chen and Wanli Liu J Immunol published online 26 April 2019 http://www.jimmunol.org/content/early/2019/04/25/jimmun ol.1900089 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2019/04/25/jimmunol.190008 Material 9.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published April 26, 2019, doi:10.4049/jimmunol.1900089 The Journal of Immunology Dlg1 Maintains Dendritic Cell Function by Securing Voltage-Gated K+ Channel Integrity Xuejiao Dong,*,1 Lisi Wei,†,1 Xueheng Guo,‡,x,1 Zhiyong Yang,{ Chuan Wu,‖ Peiyu Li,#,** Lu Lu,# Hai Qi,‡ Yan Shi,‡ Xiaoyu Hu,‡ Li Wu,‡ Liangyi Chen,† and Wanli Liu* Dendritic cells (DCs) play key roles in Ab responses by presenting Ags to lymphocytes and by producing proinflammatory cytokines. In this study, we reported that DC-specific knockout of discs large homologue 1 (Dlg1) resulted in a significantly reduced capacity to mediate Ab responses to both thymus-independent and thymus-dependent Ags in Dlg1fl/flCd11c-Cre-GFP mice. Mechanistically, Dlg1-deficient DCs showed severely impaired endocytosis and phagocytosis capacities upon Ag exposure. In parallel, loss of Dlg1 significantly jeopardized the proinflammatory cytokine production by DCs upon TLR stimulation. Thus, Dlg1-deficient DCs lost their functions to support innate and adaptive immunities. At a cellular level, Dlg1 exhibited an indispensable function to maintain Downloaded from membrane potential changes by securing potassium ion (K+) efflux and subsequent calcium ion (Ca2+) influx events in DCs upon stimulation, both of which are known to be required for proper function of DCs. At a molecular level, Dlg1 did so by retaining the integrity of voltage-gated K+ channels (including Kv1.3) in DCs. The loss of Dlg1 led to a decreased expression of K+ channels, resulting in impaired membrane potential changes and, as a consequence, reduced proinflammatory cytokine production, com- promised Ag endocytosis, and phagocytosis. In conclusion, this study provided, to our knowledge, a novel insight into Dlg1 and the voltage-gated K+ channels axis in DC functions. The Journal of Immunology, 2019, 202: 000–000. http://www.jimmunol.org/ he production of Abs is an important function of human immunological synapse is a typical highly polarized membrane adaptive immunity. Dendritic cells (DCs), a link between structure, the formation of which involves the occurrence of T innate and adaptive immunities, play key roles in Ab molecular events to remodel the cytoskeleton and recruit a responses by capturing and presenting Ags to lymphocytes and series of serine-threonine kinases, lipid kinases, and adaptor pro- by producing proinflammatory cytokines upon Ag stimulation teins, suggesting the highly dynamic nature of DC immunological (1). DCs can be classified into several distinct subsets, consisting synapse (4). of CD8a+ conventional DCs (cDCs), CD11b+ cDCs, and plas- The Scribble complex, which is composed of Scribble, discs by guest on September 24, 2021 macytoid DCs (pDCs), according to their cell surface markers, large (Dlg), and lethal giant larvae, is known to play key roles in anatomic locations, or immunological functions (2). Under physi- highly polarized membrane structures, including epithelial cell ological conditions, DCs usually form dynamic cell–cell contacts junctions, neuronal synapses, B cell synapses, and T cell synapses when performing their functions (3–5), which have been de- (6–9). There are four members in the Dlg family, which are discs scribed as a specialized membrane structure named immuno- large homologue 1 (Dlg1) (SAP-97), Dlg2 (PSD-93), Dlg3 (SAP- logical synapse. In DC–T cell contacts, DCs present Ags to 102, NE-Dlg), and Dlg4 (PSD-95) (10). The Dlg family belongs to T cells and fine-tune T cell activation via surface receptors, co- the membrane-associated guanylate kinase (MAGUK) superfamily, stimulatory molecules, and secreted cytokines (3, 4). Ag-bearing consisting of three PDZ domains, a single L27 domain, a single DCs can also activate B cells by cell–cell contacts (5). DC SH3 domain, and a guanylate kinase domain (11). In neurons, *Ministry of Education Key Laboratory of Protein Sciences, Center for Life Sci- the National Natural Science Foundation of China (31330027 and 91642207) and a ences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious National Key Basic Research Grant from the Ministry of Science and Technology of Diseases, School of Life Sciences, Beijing Key Laboratory for Immunological China (2015CB943200). This work was also supported by the National Multiple Research on Chronic Diseases, Institute for Immunology, Tsinghua University, Sclerosis Society (Career Transition Award TA 30 59 -A-2 to C.W.). Beijing 100084, China; †State Key Laboratory of Membrane Biology, Beijing Address correspondence and reprint requests to Dr. Wanli Liu and Prof. Li Wu or Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Dr. Liangyi Chen, School of Life Sciences, Tsinghua University, Beijing 100084, Medicine, Peking University, Beijing 100871, China; ‡Institute for Immunology, x China (W.L.) and School of Medicine, Tsinghua University, Beijing 100084, China School of Medicine, Tsinghua University, Beijing 100084, China; National { (L. Wu) or State Key Laboratory of Membrane Biology, Beijing Key Laboratory Education Examinations Authority, Beijing 100084, China; Cardiovascular Re- of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking search Institute, University of California, San Francisco, San Francisco, CA 94143; ‖ University, Beijing 100871, China (L.C.). E-mail addresses: [email protected] Experimental Immunology Branch, National Cancer Institute, National Institutes of (W.L.) and [email protected] (L. Wu) or [email protected] (L.C.) Health, Bethesda, MD 20851; #Key Laboratory of Medical Molecular Virology of the Ministry of Education/Ministry of Health, School of Basic Medical Sciences and The online version of this article contains supplemental material. Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China; Abbreviations used in this article: AF647, Alexa Fluor 647; BMC, bone marrow cell; **Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous BMDC, bone marrow–derived DC; BP, biological process; cDC, conventional DC; Infections, Shenzhen Nanshan People’s Hospital, Guangdong Medical University, DC, dendritic cell; Dlg, discs large; Dlg1, discs large homologue 1; GO, gene on- Shenzhen 518052, China tology; KO, knockout; MHC-II, MHC class II; MS, mass spectrometry; NP, 4- 1 X.D., L. Wei, and X.G. contributed equally. hydroxy-3-nitrophenylacetic; NP33-KLH, 4-hydroxy-3-nitrophenylacetyl 33–keyhole limpet hemocyanin; pDC, plasmacytoid DC; TD, thymus-dependent; TI, thymus- ORCIDs: 0000-0003-0589-6224 (Z.Y.); 0000-0002-1001-7485 (P.L.); 0000-0001- independent; WT, wild-type. 5475-3989 (H.Q.); 0000-0003-0395-2800 (W.L.). Received for publication February 4, 2019. Accepted for publication April 1, 2019. Copyright Ó 2019 by The American Association of Immunologists, Inc. 0022-1767/19/$37.50 This work was supported by funds from the National Natural Science Foundation of China (81825010, 81730043, 81621002, and 31811540397). L. Wu is supported by www.jimmunol.org/cgi/doi/10.4049/jimmunol.1900089 2 Dlg1 SECURES DENDRITIC CELL FUNCTION Dlg1 has been shown to play important roles in controlling signal Flow cytometry strength and neuron receptor density through its interaction with Single-cell suspensions were prepared. Cells were first blocked by using cytoplasmic tails of neuronal a-amino-3-hydroxy-5-methyl-4- CD16/32 Ab (clone 2.4G2) and then were stained with a combination of isoxazolepropionic acid receptor (AMPA) or N-methyl-D-aspartic the following Abs purchased from eBioscience and BioLegend: anti-CD11c acid receptor (NMDA) at neuronal synapses (11). In immuno- (N418), anti-CD95 (15A7), anti–Siglec H (eBio440c), anti-CD8a (53-6.7), logical studies, Dlg1 has been implicated in the functions of anti-F4/80 (T45-2342), anti-CD11b (M1/70), anti-CD103 (2E7), anti-MHC class II (MHC-II; M5/114.15.2), anti-CD24 (M1/69), anti-CD80 (16-10A1), B cells and T cells, such as stabilizing the phosphatase and tensin anti-CD86 (GL1), anti-B220 (RA3-6B2), anti-GL7 (GL-7), and anti-TLR4 homolog (PTEN) to suppress AKT activation (12) and recruiting (SA15-21). An LSRFortessa (BD Biosciences) was
Load more

Recommended publications
  • Likely Pathogenic Variants in One Third of Non-Syndromic Discontinuous Cleft Lip and Palate Patients
    G C A T T A C G G C A T genes Article Likely Pathogenic Variants in One Third of Non-Syndromic Discontinuous Cleft Lip and Palate Patients Bénédicte Demeer 1,2,3,4 , Nicole Revencu 1,5, Raphael Helaers 1 , Cica Gbaguidi 6, Stéphanie Dakpe 3,4,6 , Geneviève François 7, Bernard Devauchelle 3,4,6,Bénédicte Bayet 8 and Miikka Vikkula 1,* 1 Human Molecular Genetics, de Duve Institute, University of Louvain, 1200 Brussels, Belgium; [email protected] (B.D.); [email protected] (N.R.); [email protected] (R.H.) 2 Center for Human Genetics, CLAD Nord de France, CHU Amiens-Picardie, 80054 Amiens, France 3 Université Picardie Jules Verne, EA CHIMERE, EA 7516, 80054 Amiens, France; [email protected] (S.D.); [email protected] (B.D.) 4 Facing Faces Institute, 80054 Amiens, France 5 Center for Human Genetics, Cliniques universitaires Saint-Luc, University of Louvain, 1200 Brussels, Belgium 6 Department of Maxillofacial Surgery and Stomatology, Centre de Compétence Fentes et Malformations Faciales (MAFACE), CHU Amiens-Picardie, 80054 Amiens, France; [email protected] 7 Department of Pediatrics, Cliniques Universitaires Saint-Luc, University of Louvain, 1200 Brussels, Belgium; [email protected] 8 Centre Labiopalatin, Division of Plastic Surgery, Cliniques Universitaires Saint-Luc, University of Louvain, 1200 Brussels, Belgium; [email protected] * Correspondence: [email protected]; Tel.: +32-2-764-7490 Received: 6 September 2019; Accepted: 19 October 2019; Published: 22 October 2019 Abstract: Oral clefts are composed of cleft of the lip, cleft of the lip and palate, or cleft of the palate, and they are associated with a wide range of expression and severity.
    [Show full text]
  • Chr21 Protein-Protein Interactions: Enrichment in Products Involved in Intellectual Disabilities, Autism and Late Onset Alzheimer Disease
    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.11.872606; this version posted December 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Chr21 protein-protein interactions: enrichment in products involved in intellectual disabilities, autism and Late Onset Alzheimer Disease Julia Viard1,2*, Yann Loe-Mie1*, Rachel Daudin1, Malik Khelfaoui1, Christine Plancon2, Anne Boland2, Francisco Tejedor3, Richard L. Huganir4, Eunjoon Kim5, Makoto Kinoshita6, Guofa Liu7, Volker Haucke8, Thomas Moncion9, Eugene Yu10, Valérie Hindie9, Henri Bléhaut11, Clotilde Mircher12, Yann Herault13,14,15,16,17, Jean-François Deleuze2, Jean- Christophe Rain9, Michel Simonneau1, 18, 19, 20** and Aude-Marie Lepagnol- Bestel1** 1 Centre Psychiatrie & Neurosciences, INSERM U894, 75014 Paris, France 2 Laboratoire de génomique fonctionnelle, CNG, CEA, Evry 3 Instituto de Neurociencias CSIC-UMH, Universidad Miguel Hernandez-Campus de San Juan 03550 San Juan (Alicante), Spain 4 Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA 5 Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 34141, Republic of Korea 6 Department of Molecular Biology, Division of Biological Science, Nagoya University Graduate School of Science, Furo, Chikusa, Nagoya, Japan 7 Department of Biological Sciences, University of Toledo, Toledo, OH, 43606, USA 8 Leibniz Forschungsinstitut für Molekulare Pharmakologie
    [Show full text]
  • Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment Via CREB-BDNF Signalling
    International Journal of Molecular Sciences Article Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment via CREB-BDNF Signalling Matteo Spinelli 1, Francesca Natale 1,2, Marco Rinaudo 1, Lucia Leone 1,2, Daniele Mezzogori 1, Salvatore Fusco 1,2,* and Claudio Grassi 1,2 1 Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; [email protected] (M.S.); [email protected] (F.N.); [email protected] (M.R.); [email protected] (L.L.); [email protected] (D.M.); [email protected] (C.G.) 2 Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy * Correspondence: [email protected] Received: 6 October 2020; Accepted: 25 November 2020; Published: 26 November 2020 Abstract: Overnutrition and metabolic disorders impair cognitive functions through molecular mechanisms still poorly understood. In mice fed with a high fat diet (HFD) we analysed the expression of synaptic plasticity-related genes and the activation of cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signalling. We found that a HFD inhibited both CREB phosphorylation and the expression of a set of CREB target genes in the hippocampus. The intranasal administration of neural stem cell (NSC)-derived exosomes (exo-NSC) epigenetically restored the transcription of Bdnf, nNOS, Sirt1, Egr3, and RelA genes by inducing the recruitment of CREB on their regulatory sequences. Finally, exo-NSC administration rescued both BDNF signalling and memory in HFD mice. Collectively, our findings highlight novel mechanisms underlying HFD-related memory impairment and provide evidence of the potential therapeutic effect of exo-NSC against metabolic disease-related cognitive decline.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Clinical Application of Chromosomal Microarray Analysis for Fetuses With
    Xu et al. Molecular Cytogenetics (2020) 13:38 https://doi.org/10.1186/s13039-020-00502-5 RESEARCH Open Access Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations Chenyang Xu1†, Yanbao Xiang1†, Xueqin Xu1, Lili Zhou1, Huanzheng Li1, Xueqin Dong1 and Shaohua Tang1,2* Abstract Background: The potential correlations between chromosomal abnormalities and craniofacial malformations (CFMs) remain a challenge in prenatal diagnosis. This study aimed to evaluate 118 fetuses with CFMs by applying chromosomal microarray analysis (CMA) and G-banded chromosome analysis. Results: Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic copy number variations (CNVs) only (10/118; 8.5%).We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes including TBX1, MAPK1, PCYT1A, DLG1, LHX1, SHH, SF3B4, FOXC1, ZIC2, CREBBP, SNRPB, and CSNK2A1. Conclusion: These findings enrich our understanding of the potential causative CNVs and genes in CFMs. Identification of the genetic basis of CFMs contributes to our understanding of their pathogenesis and allows detailed genetic counselling.
    [Show full text]
  • Downloads/ (Accessed on 17 January 2020)
    cells Review Novel Approaches for Identifying the Molecular Background of Schizophrenia Arkadiy K. Golov 1,2,*, Nikolay V. Kondratyev 1 , George P. Kostyuk 3 and Vera E. Golimbet 1 1 Mental Health Research Center, 34 Kashirskoye shosse, 115522 Moscow, Russian; [email protected] (N.V.K.); [email protected] (V.E.G.) 2 Institute of Gene Biology, Russian Academy of Sciences, 34/5 Vavilova Street, 119334 Moscow, Russian 3 Alekseev Psychiatric Clinical Hospital No. 1, 2 Zagorodnoye shosse, 115191 Moscow, Russian; [email protected] * Correspondence: [email protected] Received: 5 November 2019; Accepted: 16 January 2020; Published: 18 January 2020 Abstract: Recent advances in psychiatric genetics have led to the discovery of dozens of genomic loci associated with schizophrenia. However, a gap exists between the detection of genetic associations and understanding the underlying molecular mechanisms. This review describes the basic approaches used in the so-called post-GWAS studies to generate biological interpretation of the existing population genetic data, including both molecular (creation and analysis of knockout animals, exploration of the transcriptional effects of common variants in human brain cells) and computational (fine-mapping of causal variability, gene set enrichment analysis, partitioned heritability analysis) methods. The results of the crucial studies, in which these approaches were used to uncover the molecular and neurobiological basis of the disease, are also reported. Keywords: schizophrenia; GWAS; causal genetic variants; enhancers; brain epigenomics; genome/epigenome editing 1. Introduction Schizophrenia is a severe mental illness that affects between 0.5% and 0.7% of the human population [1]. Both environmental and genetic factors are thought to be involved in its pathogenesis, with genetic factors playing a key role in disease risk, as the heritability of schizophrenia is estimated to be 70–85% [2,3].
    [Show full text]
  • T Cells + Cytokines in CD8 Activation and Induction of Proinflammatory
    Selective Phosphorylation of the Dlg1AB Variant Is Critical for TCR-Induced p38 Activation and Induction of Proinflammatory Cytokines in CD8 + T Cells This information is current as of September 29, 2021. Jillian Crocetti, Oscar Silva, Lisa A. Humphries, Michelle D. Tibbs and M. Carrie Miceli J Immunol 2014; 193:2651-2660; Prepublished online 6 August 2014; doi: 10.4049/jimmunol.1401196 Downloaded from http://www.jimmunol.org/content/193/6/2651 References This article cites 49 articles, 25 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/193/6/2651.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 29, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Author Choice Freely available online through The Journal of Immunology Author Choice option Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Selective Phosphorylation of the Dlg1AB Variant Is Critical for TCR-Induced p38 Activation and Induction of Proinflammatory Cytokines in CD8+ T Cells Jillian Crocetti,*,1 Oscar Silva,†,1 Lisa A.
    [Show full text]
  • BDNF Integrity in Ageing and Stress
    MOJ Gerontology & Geriatrics Editorial Open Access BDNF integrity in ageing and stress Editorial Volume 1 Issue 6 - 2017 Alzheimer’s disease (AD) presents a progressive, stage-dependent Trevor Archer age-related neurodegenerative disorder that is characterized by Department of Psychology, University of Gothenburg, Sweden aggregation of toxic forms of amyloid β peptide (Aβ). There is much support for the notion that that brain-derived neurotrophic factor Correspondence: Trevor Archer, Department of Psychology, (BDNF) mediates beneficial effects of exercise on neuroplasticity and University of Gothenburg, Sweden, cellular stress resistance.1‒3 BDNF is associated with neuroplasticity Email [email protected] changes promoting health and well-being whereas these influences Received: July 16, 2017 | Published: August 01, 2017 may be opposed by pro-inflammatory cytokines, key factors in neurodegenerative processes.4 Lower serum levels are linked to greater symptom, cognitive, impairment.5 Thus, interventions, as for example physical exercise, whether acute or chronic, endurance or resistance, promote the mobilization of BDNF and other neurotrophic factors6,7 increase hippocampal and other brain regional resilience8 and therewith progression under conditions of stress when confronted critical life protect against cell death by inducing cell proliferation and maturation episodes or periods, appears to be modulated by the availability and with enhanced neuronal reparation, neurogenesis and the growth and accessibility of BDNF.20‒22 Over a wide range of neurologic and functioning of neurons in neurodegenerative disorders.9,10 Sampaio et psychiatric disease states it is found that the integrity and concentrations al.11 in a review of the therapeutic applications of neurotrophic factors, of brain, serum and plasma BDNF is compromised, particularly under particularly BDNF, postulate that they are essential for survival, stressful conditions.
    [Show full text]
  • Supplementary Table 8. Cpcp PPI Network Details for Significantly Changed Proteins, As Identified in 3.2, Underlying Each of the Five Functional Domains
    Supplementary Table 8. cPCP PPI network details for significantly changed proteins, as identified in 3.2, underlying each of the five functional domains. The network nodes represent each significant protein, followed by the list of interactors. Note that identifiers were converted to gene names to facilitate PPI database queries. Functional Domain Node Interactors Development and Park7 Rack1 differentiation Kcnma1 Atp6v1a Ywhae Ywhaz Pgls Hsd3b7 Development and Prdx6 Ncoa3 differentiation Pla2g4a Sufu Ncf2 Gstp1 Grin2b Ywhae Pgls Hsd3b7 Development and Atp1a2 Kcnma1 differentiation Vamp2 Development and Cntn1 Prnp differentiation Ywhaz Clstn1 Dlg4 App Ywhae Ywhab Development and Rac1 Pak1 differentiation Cdc42 Rhoa Dlg4 Ctnnb1 Mapk9 Mapk8 Pik3cb Sod1 Rrad Epb41l2 Nono Ltbp1 Evi5 Rbm39 Aplp2 Smurf2 Grin1 Grin2b Xiap Chn2 Cav1 Cybb Pgls Ywhae Development and Hbb-b1 Atp5b differentiation Hba Kcnma1 Got1 Aldoa Ywhaz Pgls Hsd3b4 Hsd3b7 Ywhae Development and Myh6 Mybpc3 differentiation Prkce Ywhae Development and Amph Capn2 differentiation Ap2a2 Dnm1 Dnm3 Dnm2 Atp6v1a Ywhab Development and Dnm3 Bin1 differentiation Amph Pacsin1 Grb2 Ywhae Bsn Development and Eef2 Ywhaz differentiation Rpgrip1l Atp6v1a Nphp1 Iqcb1 Ezh2 Ywhae Ywhab Pgls Hsd3b7 Hsd3b4 Development and Gnai1 Dlg4 differentiation Development and Gnao1 Dlg4 differentiation Vamp2 App Ywhae Ywhab Development and Psmd3 Rpgrip1l differentiation Psmd4 Hmga2 Development and Thy1 Syp differentiation Atp6v1a App Ywhae Ywhaz Ywhab Hsd3b7 Hsd3b4 Development and Tubb2a Ywhaz differentiation Nphp4
    [Show full text]
  • Loss of RET Promotes Mesenchymal Identity in Neuroblastoma Cells
    cancers Article Loss of RET Promotes Mesenchymal Identity in Neuroblastoma Cells Joachim T. Siaw 1,†, Jonatan L. Gabre 1,2,† , Ezgi Uçkun 1 , Marc Vigny 3, Wancun Zhang 4, Jimmy Van den Eynden 2 , Bengt Hallberg 1 , Ruth H. Palmer 1 and Jikui Guan 1,4,* 1 Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-40530 Gothenburg, Sweden; [email protected] (J.T.S.); [email protected] (J.L.G.); [email protected] (E.U.); [email protected] (B.H.); [email protected] (R.H.P.) 2 Anatomy and Embryology Unit, Department of Human Structure and Repair, Ghent University, 9000 Ghent, Belgium; [email protected] 3 Université Pierre et Marie Curie, UPMC, INSERM UMRS-839, 75005 Paris, France; [email protected] 4 Department of Pediatric Oncology Surgery, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Simple Summary: The anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET) receptor tyrosine kinases (RTKs) are expressed in both the developing neural crest and the pediatric cancer neuroblastoma. Moreover, ALK is mutated in approximately 10% of neuroblastomas. Here, we investigated ALK and RET in neuroblastoma, with the aim of better understanding their respective contributions. Using neuroblastoma cell lines, we show that ALK modulates RET signaling at the level of RET phosphorylation, as well as at the level of transcription. Using CRISPR/Cas9, we generated Citation: Siaw, J.T.; Gabre, J.L.; Uçkun, E.; Vigny, M.; Zhang, W.; Van RET knockout neuroblastoma cell lines and performed a multi-omics approach, combining RNA-Seq den Eynden, J.; Hallberg, B.; Palmer, and proteomics to characterize the effect of deleting RET in a neuroblastoma context.
    [Show full text]
  • LGI1–ADAM22–MAGUK Configures Transsynaptic Nanoalignment for Synaptic Transmission and Epilepsy Prevention
    LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention Yuko Fukataa,b,1, Xiumin Chenc,d,1, Satomi Chikenb,e, Yoko Hiranoa,f, Atsushi Yamagatag, Hiroki Inahashia, Makoto Sanboh, Hiromi Sanob,e, Teppei Gotoh, Masumi Hirabayashib,h, Hans-Christian Kornaui,j, Harald Prüssi,k, Atsushi Nambub,e, Shuya Fukail, Roger A. Nicollc,d,2, and Masaki Fukataa,b,2 aDivision of Membrane Physiology, Department of Molecular and Cellular Physiology, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi 444-8787, Japan; bDepartment of Physiological Sciences, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Aichi 444-8585, Japan; cDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158; dDepartment of Physiology, University of California, San Francisco, CA 94158; eDivision of System Neurophysiology, Department of System Neuroscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi 444-8585, Japan; fDepartment of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; gLaboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Kanagawa 230-0045, Japan; hCenter for Genetic Analysis of Behavior, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Okazaki 444-8787, Japan; iGerman Center for Neurodegenerative Diseases (DZNE), 10117 Berlin, Germany; jNeuroscience Research Center, Cluster NeuroCure, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany; kDepartment of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany; and lDepartment of Chemistry, Graduate School of Science, Kyoto University, 606-8502 Kyoto, Japan Contributed by Roger A. Nicoll, December 1, 2020 (sent for review October 29, 2020; reviewed by David S.
    [Show full text]
  • Host Cell Factors Necessary for Influenza a Infection: Meta-Analysis of Genome Wide Studies
    Host Cell Factors Necessary for Influenza A Infection: Meta-Analysis of Genome Wide Studies Juliana S. Capitanio and Richard W. Wozniak Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta Abstract: The Influenza A virus belongs to the Orthomyxoviridae family. Influenza virus infection occurs yearly in all countries of the world. It usually kills between 250,000 and 500,000 people and causes severe illness in millions more. Over the last century alone we have seen 3 global influenza pandemics. The great human and financial cost of this disease has made it the second most studied virus today, behind HIV. Recently, several genome-wide RNA interference studies have focused on identifying host molecules that participate in Influen- za infection. We used nine of these studies for this meta-analysis. Even though the overlap among genes identified in multiple screens was small, network analysis indicates that similar protein complexes and biological functions of the host were present. As a result, several host gene complexes important for the Influenza virus life cycle were identified. The biological function and the relevance of each identified protein complex in the Influenza virus life cycle is further detailed in this paper. Background and PA bound to the viral genome via nucleoprotein (NP). The viral core is enveloped by a lipid membrane derived from Influenza virus the host cell. The viral protein M1 underlies the membrane and anchors NEP/NS2. Hemagglutinin (HA), neuraminidase Viruses are the simplest life form on earth. They parasite host (NA), and M2 proteins are inserted into the envelope, facing organisms and subvert the host cellular machinery for differ- the viral exterior.
    [Show full text]