DOCSLIB.ORG

Calcium Control of Neurotransmitter Release

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Calcium Control of Neurotransmitter Release Downloaded from http://cshperspectives.cshlp.org/ on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Calcium Control of Neurotransmitter Release Thomas C. Su¨dhof Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305 Correspondence: [email protected] Upon entering a presynaptic terminal, an action potential opens Ca2þ channels, and transiently increases the local Ca2þ concentration at the presynaptic active zone. Ca2þ then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmins Ca2þ. Synaptotagmins bind Ca2þ via two C2-domains, and transduce the Ca2þ signal into a nanomechanical activation of the membrane fusion machinery; this acti- vation is mediated by the Ca2þ-dependent interaction of the synaptotagmin C2-domains with phospholipids and SNARE proteins. In triggering exocytosis, synaptotagmins do not act alone, but require an obligatory cofactor called complexin, a small protein that binds to SNARE complexes and simultaneously activates and clamps the SNARE complexes, thereby positioning the SNARE complexes for subsequent synaptotagmin action. The con- served function of synaptotagmins and complexins operates generally in most, if not all, Ca2þ-regulated forms of exocytosis throughout the body in addition to synaptic vesicle exo- cytosis, including in the degranulation of mast cells, acrosome exocytosis in sperm cells, hormone secretion from endocrine cells, and neuropeptide release. ynaptic transmission is initiated when an in the brainstem (Fig. 1B; reviewed in Mein- Saction potential invades a nerve terminal, renken et al. 2003). Overall, these high-resolution opening Ca2þ channels, which gate a highly electrophysiological studies on neurotrans- localized, transient increase in intracellular mitter release revealed that a presynaptic action Ca2þ at the active zone (Fig. 1A). Ca2þ triggers potential is tightly coupled to Ca2þ influx and synaptic vesicle exocytosis, thereby releasing the synaptic vesicle fusion, such that under phys- neurotransmitters contained in the vesicles and iological conditions, Ca2þ triggers fusion in a initiating synaptic transmission. This funda- few hundred microseconds, or possibly even mental mechanism was discovered in pioneer- in less than 100 microseconds (Sabatini and ing work on the neuromuscular junction by Regehr 1996). Katz and Miledi (1967). Its precise time course The amazing speed and precision of Ca2þ- was studied in many “model” synapses, includ- triggered neurotransmitter release raised the ing giant squid axon synapses (Augustine et al. question of how such speed might be possi- 1985) and rat cerebellar parallel fiber synapses ble—how can Ca2þ induce exocytosis in a few (Sabatini and Regehr 1996), but characterized hundred microseconds, on the same timescale in greatest detail in the calyx of Held synapses as the gating of an ion channel? As we will Editors: Morgan Sheng, Bernardo Sabatini, and Thomas Su¨dhof Additional Perspectives on The Synapse available at www.cshperspectives.org Copyright # 2011 Cold Spring Harbor Laboratory Press; all rights reserved. Advanced Online Article. Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a011353 1 Downloaded from http://cshperspectives.cshlp.org/ on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press T.C. Su¨dhof A Synapse Presynaptic terminal Synaptic Mitochondria vesicles Endosomes Ca2+ Postsynaptic density Receptors Postsynaptic Recycling vesiclesspine Endosomes B Presynaptic action potential (APpre) 25 mV AP Gating Ca2+-channels 0.3 msec pre 2+ Ca -Current (ICa2+) –0.5 nA ICa2+ 2+ Ca -triggered 0.5 msec Fusion pore opening Exocytosis (plotted as release rate) Release 0.5 ms–1 Neurotransmitter rate binding to 0.4 msec postsynaptic receptors –2 nA Evoked postsynaptic current (EPSC) Summation of EPSCs 0.1 msec triggers action potential EPSC Postsynaptic action 25 mV Potential (APpost) APpost 0.5 msec Figure 1. Principle and time course of Ca2þ-triggered synaptic transmission. (A) Schematic diagram of a synapse illustrating the localized influx of Ca2þ at the active zone (red ¼ secreted neurotransmitters). (B) Schematic illustration of the sequence and time course of synaptic transmission as measured by simultaneous pre- and postsynaptic patch-clamp recordings at the calyx of Held synapse. Note that Ca2þ currents and EPSC are shown inverted. (Images are modified from Su¨dhof 2004 and Meinrenken et al. 2003.) 2 Advanced Online Article. Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a011353 Downloaded from http://cshperspectives.cshlp.org/ on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Calcium Control of Neurotransmitter Release describe in this review, the speed and precision majority of the protein (Fig. 2A; Perin et al. of release are mediated, at least in part, by the 1990). Sixteen genes encoding canonical Syts properties of the Ca2þ sensor synaptotagmin are expressed in mammals; in addition, mam- (Syt) and its cofactor complexin. Moreover, in- mals contain a Syt-related gene encoding a creasing evidence indicates that the principal similar protein (the so-called B/K protein) mechanism of Ca2þ-triggered exocytosis, al- that lacks a transmembrane region, and is occa- though not the organization of this mechanism, sionally called Syt17. Synaptotagmins are evo- is conserved in other, slower forms of Ca2þ- lutionarily conserved, and invertebrates also induced exocytosis. Thus, the Syt-based fusion express multiple Syt isoforms. However, synap- apparatus emerges as a general paradigm that totagmins are absent from plants and unicellu- accounts for most Ca2þ-regulated exocytosis in lar eukaryotes, suggesting that they evolved at eukaryotic cells. the same time as animals. Moreover, a large In addition to normal action potential- family of Syt-like proteins is expressed in ani- evoked neurotransmitter release, synapses ex- mals; these proteins also contain two C2- hibit two additional forms of Ca2þ-dependent domains, but will not be discussed here further synaptic exocytosis: spontaneous “mini” release (see Pang and Su¨dhof 2010). Syt1, Syt2, Syt9, and asynchronous release (Pang and Su¨dhof and Syt12 are present on synaptic vesicles and 2010). Spontaneous mini release was discovered on secretory granules in neuroendocrine cells; by Katz (Fatt and Katz 1952), and is thought to the latter also contain Syt7. In addition, Syt10 represent the background activity of a nerve ter- was recently found on secretory vesicles con- minal that is triggered by spontaneous Ca2þ taining IGF-1 in olfactory mitral neurons (Cao fluctuations. Although the biological signifi- et al. 2011); Syt4 was localized to the trans-Golgi cance of spontaneous release remains debated, complex, synaptic vesicles, and postsynaptic its presence can be observed in all neurons. organelles, and may be widely distributed in When calculated on a per-synapse basis, spon- neuronal organelles (reviewed in Su¨dhof taneous release occurs only once every 2– 2004); and Syt7 was additionally localized to 3 hours at an individual excitatory synapse “secretory lysosomes” in nonneuronal and non- of a pyramidal neuron in the CA1 region of endocrine cells (Andrews and Chakrabarti the hippocampus, and approximately once 2005). Other Syts appear to be primarily local- every 3 min at individual inhibitory synapses. ized to transport vesicles, although some Syt Asynchronous release is undetectable in most isoforms are enriched on the plasma membrane synapses under physiological conditions, but (Butz et al. 1999), and the identity of many of becomes apparent when the principal Syt the Syt-containing vesicles remains unknown. Ca2þ sensor for regular release is ablated (Gep- C2-domains were named as sequence pert et al. 1994). Some inhibitory synapses motifs in protein kinase C isoforms (Coussens exhibit a slow form of release on repetitive stim- et al. 1986), but their functional activity as ulation (Hefft and Jonas 2005), which may autonomously folded Ca2þ-binding domains represent either genuine physiological asyn- was first identified in Syt1 (Davletov and chronous release or simply synaptotagmin- Su¨dhof 1993). The atomic structures of the dependent delayed release. C2A-domain of Syt1, the first C2-domain struc- ture determined (Sutton et al. 1995), revealed that C2-domains are composed of a stable STRUCTURE AND BIOCHEMICAL b-sandwich with flexible loops emerging from PROPERTIES OF SYNAPTOTAGMINS the top and bottom (Fig. 2B); all subsequently Syts are defined as proteins containing a short determined C2-domain structures described a amino-terminal noncytoplasmic sequence fol- similar fold. Ca2þ binds exclusively to the top lowed by a transmembrane region, a central loops of the C2-domains, which form binding linker sequence of variable length, and two car- sites for two to three Ca2þ ions in close vicinity boxy-terminal C2-domains that account for the (Shao et al. 1996). Although not all C2-domains Advanced Online Article. Cite this article as Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a011353 3 Downloaded from http://cshperspectives.cshlp.org/ on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press T.C. Su¨dhof Ca2+ Ca2+ A Y Syt1, Syt2, C ACB Syt7, and Syt9 N 2 2 C Ca2+ Ca2+ N C2AC2B C Syt3, Syt5, S Syt6, and Syt10 S N C C2AC2B Ca2+ Ca2+ Syt4, Syt8, Syt11, N Syt12, Syt13, C2AC2B C Syt14, Syt15, and Syt16 B C2A-domain
Load more

Recommended publications
  • Targeted Genes and Methodology Details for Neuromuscular Genetic Panels
    Targeted Genes and Methodology Details for Neuromuscular Genetic Panels Reference transcripts based on build GRCh37 (hg19) interrogated by Neuromuscular Genetic Panels Next-generation sequencing (NGS) and/or Sanger sequencing is performed Motor Neuron Disease Panel to test for the presence of a mutation in these genes. Gene GenBank Accession Number Regions of homology, high GC-rich content, and repetitive sequences may ALS2 NM_020919 not provide accurate sequence. Therefore, all reported alterations detected ANG NM_001145 by NGS are confirmed by an independent reference method based on laboratory developed criteria. However, this does not rule out the possibility CHMP2B NM_014043 of a false-negative result in these regions. ERBB4 NM_005235 Sanger sequencing is used to confirm alterations detected by NGS when FIG4 NM_014845 appropriate.(Unpublished Mayo method) FUS NM_004960 HNRNPA1 NM_031157 OPTN NM_021980 PFN1 NM_005022 SETX NM_015046 SIGMAR1 NM_005866 SOD1 NM_000454 SQSTM1 NM_003900 TARDBP NM_007375 UBQLN2 NM_013444 VAPB NM_004738 VCP NM_007126 ©2018 Mayo Foundation for Medical Education and Research Page 1 of 14 MC4091-83rev1018 Muscular Dystrophy Panel Muscular Dystrophy Panel Gene GenBank Accession Number Gene GenBank Accession Number ACTA1 NM_001100 LMNA NM_170707 ANO5 NM_213599 LPIN1 NM_145693 B3GALNT2 NM_152490 MATR3 NM_199189 B4GAT1 NM_006876 MYH2 NM_017534 BAG3 NM_004281 MYH7 NM_000257 BIN1 NM_139343 MYOT NM_006790 BVES NM_007073 NEB NM_004543 CAPN3 NM_000070 PLEC NM_000445 CAV3 NM_033337 POMGNT1 NM_017739 CAVIN1 NM_012232 POMGNT2
    [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]
  • Effects of Neonatal Stress and Morphine on Murine Hippocampal Gene Expression
    0031-3998/11/6904-0285 Vol. 69, No. 4, 2011 PEDIATRIC RESEARCH Printed in U.S.A. Copyright © 2011 International Pediatric Research Foundation, Inc. Effects of Neonatal Stress and Morphine on Murine Hippocampal Gene Expression SANDRA E. JUUL, RICHARD P. BEYER, THEO K. BAMMLER, FEDERICO M. FARIN, AND CHRISTINE A. GLEASON Department of Pediatrics [S.E.J., C.A.G.], Department of Environmental and Occupational Health Sciences [R.P.B., T.K.B., F.M.F.], University of Washington, Seattle, Washington 98195 ABSTRACT: Critically ill preterm infants experience multiple to severe impairment occurring in close to 50% of ex- stressors while hospitalized. Morphine is commonly prescribed to tremely LBW infants (4). Autism, attention deficit disorder, ameliorate their pain and stress. We hypothesized that neonatal and school failure also occur more frequently in NICU stress will have a dose-dependent effect on hippocampal gene survivors (5). Although some degree of impairment might expression, and these effects will be altered by morphine treat- ment. Male C57BL/6 mice were exposed to five treatment condi- be inevitable, it is likely that the stress and treatments these tions between postnatal d 5 and 9: 1) control, 2) mild stress ϩ infants undergo impact neurologic outcome. Improved un- saline, 3) mild stress ϩ morphine, 4) severe stress ϩ saline, and derstanding of these factors will provide the basis of better 5) severe stress ϩ morphine. Hippocampal RNA was extracted treatments and subsequent improvement in outcomes. and analyzed using Affymetrix Mouse Gene 1.0 ST Arrays. Single Many preterm infants receive opiates for sedation or gene analysis and gene set analysis were used to compare groups analgesia during their NICU stay.
    [Show full text]
  • Synaptotagmin13 Is a Neuroendocrine Marker in Brain, Intestine and Pancreas
    Synaptotagmin13 Is A Neuroendocrine Marker In Brain, Intestine And Pancreas Marta Tarquis-Medina Helmholtz Zentrum München Katharina Scheibner Helmholtz Zentrum München Ismael Gonzalez Garcia Helmholtz Zentrum München Aimée Bastidas-Ponce Helmholtz Zentrum München Michael Sterr Helmholtz Zentrum München Jessica Jaki Helmholtz Zentrum München Silvia Schirge Helmholtz Zentrum München Cristina García-Cáceres Helmholtz Zentrum München Heiko Lickert Helmholtz Zentrum München Mostafa Bakhti ( [email protected] ) Helmholtz Zentrum München Research Article Keywords: Synaptotagmin 13, Syt13, uorescent reporter, endocrine lineage, brain, intestine, pancreas Posted Date: June 22nd, 2021 DOI: https://doi.org/10.21203/rs.3.rs-622505/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/18 Abstract Synaptotagmin13 (Syt13) is an atypical member of the vesicle tracking Synaptotagmin protein family. The expression pattern and the biological function of this Ca2+-independent protein are not well resolved. Here, we have generated a novel Syt13-Venus fusion (Syt13-VF) uorescence reporter allele to track and isolate tissues and cells expressing Syt13 protein. The reporter allele is regulated by endogenous cis- regulatory elements of Syt13 and the fusion protein follows an identical expression pattern of the endogenous Syt13 protein. The homozygous reporter mice are viable and fertile. We identify the expression of the Syt13-VF reporter in different regions of the brain with high expression in tyrosine hydroxylase (TH)-expressing and oxytocin-producing neuroendocrine cells. Moreover, Syt13-VF is highly restricted to all enteroendocrine cells in the adult intestine that can be traced in live imaging. Finally, Syt13-VF protein is expressed in the pancreatic endocrine lineage allowing their specic isolation by ow sorting.
    [Show full text]
  • Mapping Protein Interactions of Sodium Channel Nav1.7 Using 2 Epitope-Tagged Gene Targeted Mice
    bioRxiv preprint doi: https://doi.org/10.1101/118497; this version posted March 20, 2017. 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. 1 Mapping protein interactions of sodium channel NaV1.7 using 2 epitope-tagged gene targeted mice 3 Alexandros H. Kanellopoulos1†, Jennifer Koenig1, Honglei Huang2, Martina Pyrski3, 4 Queensta Millet1, Stephane Lolignier1, Toru Morohashi1, Samuel J. Gossage1, Maude 5 Jay1, John Linley1, Georgios Baskozos4, Benedikt Kessler2, James J. Cox1, Frank 6 Zufall3, John N. Wood1* and Jing Zhao1†** 7 1Molecular Nociception Group, WIBR, University College London, Gower Street, 8 London WC1E 6BT, UK. 9 2Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, The 10 Old Road Campus, Oxford, OX3 7FZ, UK. 11 3Center for Integrative Physiology and Molecular Medicine, Saarland University, 12 Kirrbergerstrasse, Bldg. 48, 66421 Homburg, Germany. 13 4Division of Bioscience, University College London, Gower Street, London WC1E 6BT, UK.14 15 †These authors contributed equally to directing this work. 16 *Correspondence author. Tel: +44 207 6796 954; E-mail: [email protected] 17 **Corresponding author: Tel: +44 207 6790 959; E-mail: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/118497; this version posted March 20, 2017. 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. 18 Abstract 19 The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. 20 Besides action potential propagation, NaV1.7 regulates neurotransmitter release, 21 integrates depolarizing inputs over long periods and regulates transcription.
    [Show full text]
  • Identification of Key Genes and Pathways Involved in Response To
    Deng et al. Biol Res (2018) 51:25 https://doi.org/10.1186/s40659-018-0174-7 Biological Research RESEARCH ARTICLE Open Access Identifcation of key genes and pathways involved in response to pain in goat and sheep by transcriptome sequencing Xiuling Deng1,2†, Dong Wang3†, Shenyuan Wang1, Haisheng Wang2 and Huanmin Zhou1* Abstract Purpose: This aim of this study was to investigate the key genes and pathways involved in the response to pain in goat and sheep by transcriptome sequencing. Methods: Chronic pain was induced with the injection of the complete Freund’s adjuvant (CFA) in sheep and goats. The animals were divided into four groups: CFA-treated sheep, control sheep, CFA-treated goat, and control goat groups (n 3 in each group). The dorsal root ganglions of these animals were isolated and used for the construction of a cDNA= library and transcriptome sequencing. Diferentially expressed genes (DEGs) were identifed in CFA-induced sheep and goats and gene ontology (GO) enrichment analysis was performed. Results: In total, 1748 and 2441 DEGs were identifed in CFA-treated goat and sheep, respectively. The DEGs identi- fed in CFA-treated goats, such as C-C motif chemokine ligand 27 (CCL27), glutamate receptor 2 (GRIA2), and sodium voltage-gated channel alpha subunit 3 (SCN3A), were mainly enriched in GO functions associated with N-methyl- D-aspartate (NMDA) receptor, infammatory response, and immune response. The DEGs identifed in CFA-treated sheep, such as gamma-aminobutyric acid (GABA)-related DEGs (gamma-aminobutyric acid type A receptor gamma 3 subunit [GABRG3], GABRB2, and GABRB1), SCN9A, and transient receptor potential cation channel subfamily V member 1 (TRPV1), were mainly enriched in GO functions related to neuroactive ligand-receptor interaction, NMDA receptor, and defense response.
    [Show full text]
  • Lipid Droplets Protect Human Β Cells from Lipotoxic-Induced Stress and Cell
    bioRxiv preprint doi: https://doi.org/10.1101/2021.06.19.449124; this version posted June 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Lipid droplets protect human β cells from lipotoxic-induced stress and cell identity changes Xin Tong1 and Roland Stein1,2 1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 2Corresponding author: [email protected]; Tel: 615-322-7026 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.19.449124; this version posted June 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract (200 words) Free fatty acids (FFAs) are often stored in lipid droplet (LD) depots for eventual metabolic and/or synthetic use in many cell types, such a muscle, liver, and fat. In pancreatic islets, overt LD accumulation was detected in humans but not mice. LD buildup in islets was principally observed after roughly 11 years of age, increasing throughout adulthood under physiologic conditions, and also enriched in type 2 diabetes. To obtain insight into the role of LDs in human islet β cell function, the levels of a key LD structural protein, perilipin2 (PLIN2), were manipulated by lentiviral-mediated knock-down (KD) or over-expression (OE) in EndoCβH2-Cre cells, a human cell line with adult islet β-like properties.
    [Show full text]
  • Figure S1. SYT1 and SYT3 Are Induced Under Abiotic Stress (Related to Figure 1)
    Figure S1. SYT1 and SYT3 are induced under abiotic stress (related to Figure 1). (A) Phylogenetic clustering of the Arabidopsis protein coding sequence of SYT1, SYT2, SYT3, SYT4, SYT5 and the Homo sapiens E-Syt1. Phylogenetic tree was inferred using the Neighbor-Joining method. The optimal tree with the sum of branch length = 3.26 is shown. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The evolutionary distances were computed using the p-distance method and are in the units of the number of amino acid differences per site. This analysis involved 11 amino acid sequences. All ambiguous positions were removed for each sequence pair (pairwise deletion option). There were a total of 1752 positions in the final dataset. Evolutionary analyses were conducted using MEGA X (Kumar et al., 2018). (B) Gene expression profiles based on RNA-seq analysis of SYT1, SYT2, SYT3, SYT4, and SYT5 in vegetative tissues at different developmental stages from TRAVA database http://travadb.org/). Each dot represent a RNAseq value and the bar represent the median. (C) Gene expression profiles based on RNA-seq analysis of SYT1, SYT3, and SYT5 in eFP-seq Browser after various abiotic stresses (https://bar.utoronto.ca/eFP-Seq_Browser/).https://bar.utoronto.ca/eFP- Seq_Browser/). (D) Heatmap representing the expression responses to abiotic stress of SYT1, SYT3 and SYT5. Expression levels genes are represented as the fold-change relative to the control. Red represents a gene that is induced, and blue represents a gene that is repressed in response to the indicated abiotic stress.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
    medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened.
    [Show full text]
  • Table 1A SIRT1 Differential Binding Gene List Down
    Rp1 Rb1cc1 Pcmtd1 Mybl1 Sgk3 Cspp1 Arfgef1 Cpa6 Kcnb2 Stau2 Jph1 Paqr8 Kcnq5 Rims1 Smap1 Bai3 Prim2 Bag2 Zfp451 Dst Uggt1 4632411B12Rik Fam178b Tmem131 Inpp4a 2010300C02Rik Rev1 Aff3 Map4k4 Il1r1 Il1rl2 Tgfbrap1 Col3a1 Wdr75 Tmeff2 Hecw2 Boll Plcl1 Satb2 Aox4 Mpp4 Gm973 Carf Nbeal1 Pard3b Ino80d Adam23 Dytn Pikfyve Atic Fn1 Smarcal1 Tns1 Arpc2 Pnkd Ctdsp1 Usp37 Acsl3 Cul3 Dock10 Col4a4 Col4a3 Mff Wdr69 Pid1 Sp110 Sp140 Itm2c 2810459M11Rik Dis3l2 Chrng Gigyf2 Ugt1a7c Ugt1a6b Hjurp A730008H23Rik Trpm8 Kif1a D1Ertd622e Pam Cntnap5b Rnf152 Phlpp1 Clasp1 Gli2 Dpp10 Tmem163 Zranb3 Pfkfb2 Pigr Rbbp5 Sox13 Ppfia4 Rabif Kdm5b Ppp1r12b Lgr6 Pkp1 Kif21b Nr5a2 Dennd1b Trove2 Pdc Hmcn1 Ncf2 Nmnat2 Lamc2 Cacna1e Xpr1 Tdrd5 Fam20b Ralgps2 Sec16b Astn1 Pappa2 Tnr Klhl20 Dnm3 Bat2l2 4921528O07Rik Scyl3 Dpt Mpzl1 Creg1 Cd247 Gm4846 Lmx1a Pbx1 Ddr2 Cd244 Cadm3 Fmn2 Grem2 Rgs7 Fh1 Wdr64 Pld5 Cep170 Akt3 Pppde1 Smyd3 Parp1 Enah Capn8 Susd4 Mosc1 Rrp15 Gpatch2 Esrrg Ptpn14 Smyd2 Tmem206 Nek2 Traf5 Hhat Cdnf Fam107b Camk1d Cugbp2 Gata3 Itih5 Sfmbt2 Itga8 Pter Rsu1 Ptpla Slc39a12 Cacnb2 Nebl Pip4k2a Abi1 Tbpl2 Pnpla7 Kcnt1 Camsap1 Nacc2 Gpsm1 Sec16a Fam163b Vav2 Olfm1 Tsc1 Med27 Rapgef1 Pkn3 Zer1 Prrx2 Gpr107 Ass1 Nup214 Bat2l Dnm1 Ralgps1 Fam125b Mapkap1 Hc Ttll11 Dennd1a Olfml2a Scai Arhgap15 Gtdc1 Mbd5 Kif5c Lypd6b Lypd6 Fmnl2 Arl6ip6 Galnt13 Acvr1 Ccdc148 Dapl1 Tanc1 Ly75 Gcg Kcnh7 Cobll1 Scn3a Scn9a Scn7a Gm1322 Stk39 Abcb11 Slc25a12 Metapl1 Pdk1 Rapgef4 B230120H23Rik Gpr155 Wipf1 Pde11a Prkra Gm14461 Pde1a Calcrl Olfr1033 Mybpc3 F2 Arhgap1 Ambra1 Dgkz Creb3l1
    [Show full text]
  • Familial Hyperkalemic Hypertension
    Disease of the Month Familial Hyperkalemic Hypertension Juliette Hadchouel,* Ce´line Delaloy,* Se´bastien Faure´,† Jean-Michel Achard,† and Xavier Jeunemaitre* *Colle`ge de France, Paris; INSERM U36, Paris; AP-HP, Department of Genetics, Hoˆpital Europe´en Georges Pompidou; University Paris-Descartes, Faculty of Medicine, Paris, France; and †Division of Nephrology and Department of Physiology, Limoges University Hospital, Limoges, France J Am Soc Nephrol 17: 208–217, 2006. doi: 10.1681/ASN.2005030314 amilial hyperkalemic hypertension (FHHt) syndrome biochemical abnormalities and age or BP, which seemed to (1,2), also known as Gordon syndrome (3) or pseudohy- depend primarily on age in affected individuals (11). This F poaldosteronism type 2 (4), is a rare inherited form of phenotypic variability, associated with sensitivity to thia- low-renin hypertension associated with hyperkalemia and hy- zides—which are widely used in hypertension—and with a low perchloremic metabolic acidosis in patients with a normal GFR probability of this rare disease’s being recognized by most (OMIM no. 145260). This monogenic form of arterial hyperten- doctors may have led to an underestimation of its frequency. sion has excited new interest since the discovery of a new, The mode of inheritance of the disease is consistent with unsuspected molecular pathway that is responsible for both the autosomal dominant transmission in most, if not all, of the biochemical abnormalities and the increase in BP observed. pedigrees reported. However, we have identified two families Genetic analysis has led to the identification of mutations in in which the parents of the affected individuals were first two genes that belong to a new family of kinases, the WNK cousins, suggesting possible autosomal recessive transmission.
    [Show full text]