Early Termination of the Shiga Toxin Transcript Generates a Regulatory Small RNA
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Goat Anti-STX1A / STX1B Antibody Peptide-Affinity Purified Goat Antibody Catalog # Af2048a
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Goat Anti-STX1A / STX1B Antibody Peptide-affinity purified goat antibody Catalog # AF2048a Specification Goat Anti-STX1A / STX1B Antibody - Product Information Application WB Primary Accession Q16623 Other Accession NP_443106, 6804, 112755, 20907 (mouse), 116470 (rat) Reactivity Mouse Predicted Human, Rat, Dog, Cow Host Goat Clonality Polyclonal Concentration 100ug/200ul Isotype IgG Calculated MW 33023 AF2048a (0.003 µg/ml) staining of Mouse Brain lysate (35 µg protein in RIPA buffer). Primary incubation was 1 hour. Detected by Goat Anti-STX1A / STX1B Antibody - Additional Information chemiluminescence. Gene ID 6804 Goat Anti-STX1A / STX1B Antibody - Background Other Names Syntaxin-1A, Neuron-specific antigen HPC-1, This gene encodes a member of the syntaxin STX1A, STX1 superfamily. Syntaxins are nervous system-specific proteins implicated in the Format 0.5 mg IgG/ml in Tris saline (20mM Tris docking of synaptic vesicles with the pH7.3, 150mM NaCl), 0.02% sodium azide, presynaptic plasma membrane. Syntaxins with 0.5% bovine serum albumin possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF Storage (N-ethylmaleimide-sensitive fusion Maintain refrigerated at 2-8°C for up to 6 protein)-Attachment protein REceptor] domain months. For long term storage store at (known as H3), and an N-terminal regulatory -20°C in small aliquots to prevent domain (Habc). Syntaxins bind synaptotagmin freeze-thaw cycles. in a calcium-dependent fashion and interact with voltage dependent calcium and potassium Precautions channels via the C-terminal H3 domain. This Goat Anti-STX1A / STX1B Antibody is for gene product is a key molecule in ion channel research use only and not for use in regulation and synaptic exocytosis. -
Epileptic Mechanisms Shared by Alzheimer's Disease
International Journal of Molecular Sciences Review Epileptic Mechanisms Shared by Alzheimer’s Disease: Viewed via the Unique Lens of Genetic Epilepsy Jing-Qiong Kang 1,2 1 Department of Neurology & Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-8552, USA; [email protected]; Tel.: +1-615-936-8399; Fax: +1-615-322-5517 2 Vanderbilt Kennedy Center of Human Development, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-8522, USA Abstract: Our recent work on genetic epilepsy (GE) has identified common mechanisms between GE and neurodegenerative diseases including Alzheimer’s disease (AD). Although both disorders are seemingly unrelated and occur at opposite ends of the age spectrum, it is likely there are shared mechanisms and studies on GE could provide unique insights into AD pathogenesis. Neurodegen- erative diseases are typically late-onset disorders, but the underlying pathology may have already occurred long before the clinical symptoms emerge. Pathophysiology in the early phase of these diseases is understudied but critical for developing mechanism-based treatment. In AD, increased seizure susceptibility and silent epileptiform activity due to disrupted excitatory/inhibitory (E/I) balance has been identified much earlier than cognition deficit. Increased epileptiform activity is likely a main pathology in the early phase that directly contributes to impaired cognition. It is an enormous challenge to model the early phase of pathology with conventional AD mouse models due to the chronic disease course, let alone the complex interplay between subclinical nonconvulsive epileptiform activity, AD pathology, and cognition deficit. We have extensively studied GE, especially with gene mutations that affect the GABA pathway such as mutations in GABAA receptors and GABA transporter Citation: Kang, J.-Q. -
(PRRT2) Regulates the Actin Cytoskeleton During Synaptogenesis
Savino et al. Cell Death and Disease (2020) 11:856 https://doi.org/10.1038/s41419-020-03073-w Cell Death & Disease ARTICLE Open Access Proline-rich transmembrane protein 2 (PRRT2) regulates the actin cytoskeleton during synaptogenesis Elisa Savino1,2, Romina Inès Cervigni1,2, Miriana Povolo1,2, Alessandra Stefanetti2, Daniele Ferrante3, Pierluigi Valente3,4, Anna Corradi3,4, Fabio Benfenati 4,5, Fabrizia Claudia Guarnieri1,2 and Flavia Valtorta 1,2 Abstract Mutations in proline-rich transmembrane protein 2 (PRRT2) have been recently identified as the leading cause of a clinically heterogeneous group of neurological disorders sharing a paroxysmal nature, including paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. To date, studies aimed at understanding its physiological functions in neurons have mainly focused on its ability to regulate neurotransmitter release and neuronal excitability. Here, we show that PRRT2 expression in non-neuronal cell lines inhibits cell motility and focal adhesion turnover, increases cell aggregation propensity, and promotes the protrusion of filopodia, all processes impinging on the actin cytoskeleton. In primary hippocampal neurons, PRRT2 silencing affects the synaptic content of filamentous actin and perturbs actin dynamics. This is accompanied by defects in the density and maturation of dendritic spines. We identified cofilin, an actin-binding protein abundantly expressed at the synaptic level, as the ultimate effector of PRRT2. Indeed, PRRT2 silencing unbalances cofilin activity leading to the formation of cofilin-actin rods along neurites. The expression of a cofilin phospho-mimetic mutant (cof-S3E) is able to rescue PRRT2-dependent defects in synapse 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; density, spine number and morphology, but not the alterations observed in neurotransmitter release. -
The Prion Protein Regulates Synaptic Transmission by Controlling the Expression of Proteins Key to Synaptic Vesicle Recycling and Exocytosis
Molecular Neurobiology (2019) 56:3420–3436 https://doi.org/10.1007/s12035-018-1293-4 The Prion Protein Regulates Synaptic Transmission by Controlling the Expression of Proteins Key to Synaptic Vesicle Recycling and Exocytosis Caterina Peggion1 & Roberto Stella2 & Francesco Chemello3 & Maria Lina Massimino4 & Giorgio Arrigoni1,5 & Stefano Cagnin3 & Giancarlo Biancotto 2 & Cinzia Franchin1,5 & Maria Catia Sorgato1,4 & Alessandro Bertoli1,6 Received: 10 May 2018 /Accepted: 1 August 2018 /Published online: 20 August 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract The cellular prion protein (PrPC), whose misfolded conformers are implicated in prion diseases, localizes to both the presynaptic membrane and postsynaptic density. To explore possible molecular contributions of PrPC to synaptic transmission, we utilized a mass spectrometry approach to quantify the release of glutamate from primary cerebellar granule neurons (CGN) expressing, or deprived of (PrP-KO), PrPC, following a depolarizing stimulus. Under the same conditions, we also tracked recycling of synaptic vesicles (SVs) in the two neuronal populations. We found that in PrP-KO CGN these processes decreased by 40 and 60%, respectively, compared to PrPC-expressing neurons. Unbiased quantitative mass spectrometry was then employed to compare the whole proteome of CGN with the two PrP genotypes. This approach allowed us to assess that, relative to the PrPC-expressing counterpart, the absence of PrPC modified the protein expression profile, including diminution of some components of SV recycling and fusion machinery. Subsequent quantitative RT-PCR closely reproduced proteomic data, indicating that PrPC is committed to ensuring optimal synaptic transmission by regulating genes involved in SV dynamics and neurotransmitter release. -
Tamoxifen Blocks Retrograde Trafficking of Shiga Toxin 1 and 2
Published Online: 26 June, 2019 | Supp Info: http://doi.org/10.26508/lsa.201900439 Downloaded from life-science-alliance.org on 26 September, 2021 Research Article Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis Andrey S Selyunin1, Steven Hutchens1, Stanton F McHardy2, Somshuvra Mukhopadhyay1 Shiga toxin 1 (STx1) and 2 (STx2), produced by Shiga toxin– retrograde intracellular trafficking (4, 5, 6, 7, 8, 9). Retrograde transport producing Escherichia coli, cause lethal untreatable disease. The of both toxins involves, sequentially, endocytosis, transit through toxins invade cells via retrograde trafficking. Direct early early endosomes and the Golgi apparatus, and delivery to the en- endosome-to-Golgi transport allows the toxins to evade degra- doplasmic reticulum from where the A subunit is translocated to the dative late endosomes. Blocking toxin trafficking, particularly at cytosol (5, 6, 7, 8, 9). Direct transport from early endosomes to the Golgi the early endosome-to-Golgi step, is appealing, but transport is critical as it allows the toxins to evade late endosomes where mechanisms of the more disease-relevant STx2 are unclear. Using proteolytic enzymes are active (5, 6, 7, 8, 9). As STx1 and STx2 must data from a genome-wide siRNA screen, we discovered that traffic to the cytosol to induce cytotoxicity, blocking toxin transport in disruption of the fusion of late endosomes, but not autopha- general, and at the early endosome-to-Golgi step in particular, has gosomes, with lysosomes blocked the early endosome-to-Golgi emerged as a promising therapeutic strategy (5, 6, 10, 11). As an ex- transport of STx2. -
High Functioning Autism with Missense
International Journal of Molecular Sciences Article High Functioning Autism with Missense Mutations in Synaptotagmin-Like Protein 4 (SYTL4) and Transmembrane Protein 187 (TMEM187) Genes: SYTL4- Protein Modeling, Protein-Protein Interaction, Expression Profiling and MicroRNA Studies Syed K. Rafi 1,* , Alberto Fernández-Jaén 2 , Sara Álvarez 3, Owen W. Nadeau 4 and Merlin G. Butler 1,* 1 Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA 2 Department of Pediatric Neurology, Hospital Universitario Quirón, 28223 Madrid, Spain 3 Genomics and Medicine, NIM Genetics, 28108 Madrid, Spain 4 Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA * Correspondence: rafi[email protected] (S.K.R.); [email protected] (M.G.B.); Tel.: +816-787-4366 (S.K.R.); +913-588-1800 (M.G.B.) Received: 25 March 2019; Accepted: 17 June 2019; Published: 9 July 2019 Abstract: We describe a 7-year-old male with high functioning autism spectrum disorder (ASD) and maternally-inherited rare missense variant of Synaptotagmin-like protein 4 (SYTL4) gene (Xq22.1; c.835C>T; p.Arg279Cys) and an unknown missense variant of Transmembrane protein 187 (TMEM187) gene (Xq28; c.708G>T; p. Gln236His). Multiple in-silico predictions described in our study indicate a potentially damaging status for both X-linked genes. Analysis of predicted atomic threading models of the mutant and the native SYTL4 proteins suggest a potential structural change induced by the R279C variant which eliminates the stabilizing Arg279-Asp60 salt bridge in the N-terminal half of the SYTL4, affecting the functionality of the protein’s critical RAB-Binding Domain. -
Distinct Functions of Syntaxin-1 in Neuronal Maintenance, Synaptic Vesicle Docking, and Fusion in Mouse Neurons
The Journal of Neuroscience, July 27, 2016 • 36(30):7911–7924 • 7911 Cellular/Molecular Distinct Functions of Syntaxin-1 in Neuronal Maintenance, Synaptic Vesicle Docking, and Fusion in Mouse Neurons Gu¨lc¸in Vardar,1,2 XShuwen Chang,1,2 Marife Arancillo,2 XYuan-Ju Wu,2 XThorsten Trimbuch,1,2 and X Christian Rosenmund1,2 1Department of Neurophysiology and 2NeuroCure Cluster of Excellence, Charite´ Universita¨tsmedizin Berlin, 10117 Berlin, Germany Neurotransmitter release requires the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes by SNARE proteins syntaxin-1 (Stx1), synaptosomal-associated protein 25 (SNAP-25), and synaptobrevin-2 (Syb2). In mam- malian systems, loss of SNAP-25 or Syb2 severely impairs neurotransmitter release; however, complete loss of function studies for Stx1 have been elusive due to the functional redundancy between Stx1 isoforms Stx1A and Stx1B and the embryonic lethality of Stx1A/1B double knock-out (DKO) mice. Here, we studied the roles of Stx1 in neuronal maintenance and neurotransmitter release in mice with constitutive or conditional deletion of Stx1B on an Stx1A-null background. Both constitutive and postnatal loss of Stx1 severely compro- mised neuronal viability in vivo and in vitro, indicating an obligatory role of Stx1 for maintenance of developing and mature neurons. Loss of Munc18-1, a high-affinity binding partner of Stx1, also showed severely impaired neuronal viability, but with a slower time course compared with Stx1A/1B DKO neurons, and exogenous Stx1A or Stx1B expression significantly delayed Munc18-1-dependent lethality. In addition, loss of Stx1 completely abolished fusion-competent vesicles and severely impaired vesicle docking, demonstrating its essential roles in neurotransmission. -
Identifying Shared Risk Genes Between Nonalcoholic Fatty Liver Disease and Metabolic Traits by Cross-Trait Association Analysis
Article Supplementary Materials: Identifying Shared Risk Genes between Nonalcoholic Fatty Liver Disease and Metabolic Traits by Cross-Trait Association Analysis Hongping Guo 1,2 and Zuguo Yu 1,3,* Table S1. Cross-trait meta-analysis result between NAFLD, obesity and T2D. SNP Genome Position A1/A2 P_RE2C Genes within Clumping Region rs7903146 chr10:114597109-114914665 T/C 6.95 × 10−206 TCF7L2 rs10811661 chr9:22130065–22134094 C/T 1.50 × 10−34 - rs1421085 chr16:53800387–53839135 C/T 4.47 × 10−34 FTO rs7651090 chr3:185473065-185547917 G/A 9.28 × 10−34 IGF2BP2 rs2206734 chr6:20529542–20766697 T/C 1.61 × 10−32 CDKAL1 rs13266634 chr8:118183551–118217307 T/C 1.79 × 10−31 SLC30A8 rs849135 chr7:28138639–28256240 G/A 1.97 × 10−26 JAZF1 rs7018475 chr9:22137685–22137685 G/T 3.23 × 10−26 - rs7923837 chr10:94232247–94499577 A/G 3.04 × 10−24 HHEX, IDE, KIF11 rs2972144 chr2:226897985–227199263 A/G 9.76 × 10−21 - rs10244051 chr7:15023729–15065467 T/G 1.49 × 10−20 - rs11708067 chr3:123065778–123131254 G/A 3.18 × 10−20 ADCY5 rs2796441 chr9:84304985–84380739 A/G 5.11 × 10−20 - rs738408 chr22:44324730–44395451 T/C 6.84 × 10−20 PARVB, PNPLA3, SAMM50 rs1128249 chr2:165501849–165558252 T/G 2.05 × 10−19 COBLL1 rs13411629 chr2:43450138–43848664 C/T 1.06 × 10−18 THADA, ZFP36L2 rs10885414 chr10:114835452–114916586 G/A 1.29 × 10−18 TCF7L2 rs1801206 chr4:6264968–6321396 C/T 2.19 × 10−18 WFS1 rs11651755 chr17:36098040-36103565 C/T 1.43 × 10−16 HNF1B rs476828 chr18:57732689–57912785 C/T 2.62 × 10−15 - rs3217992 chr9:21997872–22072719 T/C 4.67 × 10−15 CDKN2B rs703979 -
STXBP1 Encephalopathy Connecting Neurodevelopmental Disorders with Α-Synucleinopathies?
Published Ahead of Print on June 20, 2019 as 10.1212/WNL.0000000000007786 VIEWS & REVIEWS STXBP1 encephalopathy Connecting neurodevelopmental disorders with α-synucleinopathies? Vanessa Lanoue, PhD,* Ye Jin Chai, PhD,* Julie Z. Brouillet, MSc, Sarah Weckhuysen, MD, PhD, Correspondence Elizabeth E. Palmer, MD, Brett M. Collins, PhD, and Frederic A. Meunier, PhD Dr. Meunier [email protected] Neurology® 2019;93:1-10. doi:10.1212/WNL.0000000000007786 Abstract De novo pathogenic variants in STXBP1 encoding syntaxin1-binding protein (STXBP1, also known as Munc18-1) lead to a range of early-onset neurocognitive conditions, most commonly early infantile epileptic encephalopathy type 4 (EIEE4, also called STXBP1 encephalopathy), a severe form of epilepsy associated with developmental delay/intellectual disability. Other neurologic features include autism spectrum disorder and movement disorders. The pro- gression of neurologic symptoms has been reported in a few older affected individuals, with the appearance of extrapyramidal features, reminiscent of early onset parkinsonism. Understanding the pathologic process is critical to improving therapies, as currently available antiepileptic drugs have shown limited success in controlling seizures in EIEE4 and there is no precision medication approach for the other neurologic features of the disorder. Basic research shows that genetic knockout of STXBP1 or other presynaptic proteins of the exocytic machinery leads to widespread perinatal neurodegeneration. The mechanism that regulates this effect is under scrutiny but shares intriguing hallmarks with classical neurodegenerative diseases, albeit appearing early during brain development. Most critically, recent evidence has revealed that STXBP1 controls the self-replicating aggregation of α-synuclein, a presynaptic protein involved in various neurodegenerative diseases that are collectively known as synucleinopathies, in- cluding Parkinson disease. -
Proteomic Landscape of the Human Choroid–Retinal Pigment Epithelial Complex
Supplementary Online Content Skeie JM, Mahajan VB. Proteomic landscape of the human choroid–retinal pigment epithelial complex. JAMA Ophthalmol. Published online July 24, 2014. doi:10.1001/jamaophthalmol.2014.2065. eFigure 1. Choroid–retinal pigment epithelial (RPE) proteomic analysis pipeline. eFigure 2. Gene ontology (GO) distributions and pathway analysis of human choroid– retinal pigment epithelial (RPE) protein show tissue similarity. eMethods. Tissue collection, mass spectrometry, and analysis. eTable 1. Complete table of proteins identified in the human choroid‐RPE using LC‐ MS/MS. eTable 2. Top 50 signaling pathways in the human choroid‐RPE using MetaCore. eTable 3. Top 50 differentially expressed signaling pathways in the human choroid‐RPE using MetaCore. eTable 4. Differentially expressed proteins in the fovea, macula, and periphery of the human choroid‐RPE. eTable 5. Differentially expressed transcription proteins were identified in foveal, macular, and peripheral choroid‐RPE (p<0.05). eTable 6. Complement proteins identified in the human choroid‐RPE. eTable 7. Proteins associated with age related macular degeneration (AMD). This supplementary material has been provided by the authors to give readers additional information about their work. © 2014 American Medical Association. All rights reserved. 1 Downloaded From: https://jamanetwork.com/ on 09/25/2021 eFigure 1. Choroid–retinal pigment epithelial (RPE) proteomic analysis pipeline. A. The human choroid‐RPE was dissected into fovea, macula, and periphery samples. B. Fractions of proteins were isolated and digested. C. The peptide fragments were analyzed using multi‐dimensional LC‐MS/MS. D. X!Hunter, X!!Tandem, and OMSSA were used for peptide fragment identification. E. Proteins were further analyzed using bioinformatics. -
Hypothesis of a Non-SNARE-Function of Syntaxin-5 Stefan Rathjen
Hypothesis of a Non-SNARE-Function of Syntaxin-5 Stefan Rathjen To cite this version: Stefan Rathjen. Hypothesis of a Non-SNARE-Function of Syntaxin-5. Molecular biology. Université Paris Saclay (COmUE), 2017. English. NNT : 2017SACLS450. tel-02408332 HAL Id: tel-02408332 https://tel.archives-ouvertes.fr/tel-02408332 Submitted on 13 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Hypothesis on a non-SNARE function S450 of syntaxin-5 017SACL Thèse de doctorat de l'Université Paris-Saclay : 2 Préparée à « Institute Curie » NNT École doctorale n°568 Biosigne – Signalisations et reseaux integratifs en biologie Aspects moleculaires et cellulaires de la biologie Sciences de la vie et de la santé Thèse présentée et soutenue à Paris, le 12/12/2017, par Stefan Jan-Matthias RATHJEN Composition du Jury : Marc le MAIRE Président Professeur Émérite, Université Paris-Sud, CEA – UMR 9198 Thierry GALLI Rapporteur Directeur d'unité, Center of Psychiatry and Neuroscience – INSERM U894 Catherine JACKSON Rapporteur Chef d’équipe, Instutute Jaques Monod – -
Protein Names IGLC7 A0M8Q6 4 1 55,7 11,3
Supplementary material J Neurol Neurosurg Psychiatry Gene names Protein IDs Peptides Unique Sequence Mol. weight Protein names peptides coverage [%] [kDa] IGLC7 A0M8Q6 4 1 55,7 11,303 Ig lambda-7 chain C region SSC5D A1L4H1;A1L4H1-2 15 15 15,4 165,74 Soluble scavenger receptor cysteine- rich domain-containing protein SSC5D KIAA1467 A2RU67 2 2 5,3 67,038 Uncharacterized protein KIAA1467 MEGF11 A6BM72- 2 2 4,1 101,55 Multiple epidermal growth factor-like 2;A6BM72;A6BM72- domains protein 11 4;A6BM72-3 PGP A6NDG6 1 1 5,9 34,006 Phosphoglycolate phosphatase BTBD17 A6NE02 1 1 4,4 52,47 BTB/POZ domain-containing protein 17 IGLON5 A6NGN9 6 6 24,1 36,794 IgLON family member 5 RAP1B;RAP1A P61224-4;P61224- 2 2 19 16,033 Ras-related protein Rap-1b;Ras-related 3;P61224;A6NIZ1;P612 protein Rap-1b-like protein;Ras- 24-2;P62834 related protein Rap-1A IGHV1OR21-1 A6NJS3 1 1 12,5 13,37 Putative V-set and immunoglobulin domain-containing-like protein IGHV1OR21-1 SHISA7 A6NL88 1 1 2,4 56,213 Protein shisa-7 VSTM2B A6NLU5 6 6 27,4 30,297 V-set and transmembrane domain- containing protein 2B OR2AG1;OR2AG2 Q9H205;A6NM03 1 1 2,2 35,27 Olfactory receptor 2AG1;Olfactory receptor 2AG2 LRRC53 A6NM62 2 2 2,7 140,74 Leucine-rich repeat-containing protein 53 IGLL5;IGLC1 B9A064;P0CG04 9 4 46,7 23,063 Immunoglobulin lambda-like polypeptide 5;Ig lambda-1 chain C regions PRR24 C9JVW0 1 1 17,6 14,668 Proline-rich protein 24 Barschke P, et al.