DOCSLIB.ORG

Regulatory Mechanism of SNAP23 in Phagosome Formation and Maturation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regulatory Mechanism of SNAP23 in Phagosome Formation and Maturation Yonago Acta Medica ****;**(*):***–*** doi: 10.33160/yam.2020.08.001 Review Article: Special Contribution Regulatory Mechanism of SNAP23 in Phagosome Formation and Maturation Kiyotaka Hatsuzawa and Chiye Sakurai Division of Molecular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan ABSTRACT interaction activates a signaling cascade that induces Synaptosomal associated protein of 23 kDa (SNAP23), a cytoskeletal reorganization and extensive plasma plasma membrane-localized soluble N-ethylmaleimide- membrane deformation, ultimately leading to engulf- sensitive factor attachment protein receptor (SNARE), ment of the particles. The newly formed phagosomes is a ubiquitously expressed protein that is generally in- progressively mature into phagolysosomes by sequential volved in fusion of the plasma membrane and secretory fusion with endocytic compartments and lysosomes. or endosomal recycling vesicles during several types During this process, the microbicidal NADPH oxidase of exocytosis. SNAP23 is expressed in phagocytes, 2 (NOX2) complex is assembled in early phagosomes to such as neutrophils, macrophages, and dendritic cells, produce reactive oxygen species (ROS), and vacuolar- and functions in both exocytosis and phagocytosis. type H+-ATPase (V-ATPase) is recruited to the phago- This review focuses on the function of SNAP23 in im- some where it acidifies the phagosomal environment to munoglobulin G Fc receptor-mediated phagocytosis by promote lysosomal hydrolase activity.3–5 In some cases, macrophages. SNAP23 and its partner SNAREs medi- when phagosomal acidification is relatively mild, rem- ate fusion of the plasma membrane with intracellular nant peptides from the particles can serve as antigens organelles or vesicles to form phagosomes as well as to be presented by major histocompatibility complex the fusion of phagosomes with endosomes or lysosomes (MHC) class I and/or class II molecules.6, 7 Phagocytosis to induce phagosome maturation, characterized by is, therefore, an important process that contributes to reactive oxygen species production and acidification. host innate and adaptive immune responses against During these processes, SNAP23 function is regulated foreign particles. by phosphorylation. In addition, microtubule-associated Membrane fusion with intracellular vesicles and/ protein 1A/1B light chain 3 (LC3)-associated phagocy- or organelles, such as early and late endosomes, is tosis, which tightly promotes or suppresses phagosome triggered at both the foreign particle-attached site of maturation depending on the foreign target, requires the plasma membrane and the nascent phagosome.5, 8, 9 SNAP23 function. SNAP23 that is enriched on the Phagosome formation and maturation are complicated phagosome membrane during LC3-associated phago- processes that involve the fusion and fission of various cytosis may be phosphorylated or dephosphorylated, types of membranes, and the molecular mechanisms thereby enhancing or inhibiting subsequent phagosome are not yet fully understood. The purpose of this review maturation, respectively. These findings have increased is to highlight the function and regulation of synapto- our understanding of the SNAP23-associated mem- somal-associated protein 23 kDa (SNAP23), a plasma brane trafficking mechanism in phagocytes, which has Corresponding author: Kiyotaka Hatsuzawa, PhD important implications for microbial pathogenesis and [email protected] innate and adaptive immune responses. Received 2020 May 29 Accepted 2020 June 5 Key words MAP1LC3A; membrane fusion; phagocy- Online published 2020 June 25 tosis; SNAP23 protein; SNARE proteins Abbreviations: ER, endoplasmic reticulum; FcR, Fc receptor; FRET, Förster resonance energy transfer; GFP, green fluorescent protein; IFN-γ, interferon-gamma; IKK2, IκB kinase 2; LAP, Phagocytosis is a form of endocytosis that is largely LC3-associated phagocytosis; LAPosome, LAP phagosome; observed in professional phagocytes, particularly LC3, microtubule-associated proteins 1A/1B light chain 3; MHC, neutrophils, macrophages, and dendritic cells. During major histocompatibility complex; MORN2, membrane occupa- phagocytosis, foreign particles larger than 0.5 μm, tion and recognition nexus repeat-containing-2; mVenus, mono- meric Venus; NOX2, NADPH oxidase 2; PMA, phorbol 12-my- including bacteria, yeast cells, cellular debris, and other ristate 13-acetate; RB-dextran, rhodamine B-conjugated dextran; immunoglobulin (Ig) G-opsonized or complement-op- ROS, reactive oxygen species; si, small interfering; SNAP23, sonized targets, are recognized by various cell surface synaptosomal-associated protein of 23 kDa; SNARE, soluble pattern recognition receptors on the phagocytes, and N-ethylmaleimide-sensitive factor attachment protein receptor; internalized.1, 2 For example, Fc receptors (FcRs) cluster stx11, syntaxin 11; TNF-α, tumor necrosis factor alpha; TLR4, Toll-like receptor 4; VAMP, vesicle-associated membrane protein; at sites where they contact IgG-opsonized particles; this V-ATPase, vacuolar-type H+-ATPase 1 © 2020 Tottori University Medical Press K. Hatsuzawa and C. Sakurai Fig. 1. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and the SNARE complex. (A) Schematic rep- resentation of the SNARE family based on the central amino acid residue of the SNARE motif and the domain structure. (B) SNARE- mediated membrane fusion of target and vesicle membranes. VA MP, vesicle-associated membrane protein; TM, transmembrane domain. membrane-localized soluble N-ethylmaleimide-sensitive of phagocytosis by microinjection of tetanus toxin light factor attachment protein receptor (SNARE), in phago- chain (a potent neurotoxin produced by Clostridium some formation and maturation in macrophages, with a tetani) into macrophages revealed the involvement of focus on our recent research.10, 11 SNARE in this process.15 During FcR-mediated phago- cytosis, recycling endosome-localized VA M P3 (also SNARE PROTEINS INVOLVED IN PHAGOCYTOSIS called cellubrevin), a target of tetanus toxin light chain, Fusion between two membranes, such as a vesicle accumulates around incomplete phagosomes that have and a target membrane, is mediated by SNAREs that not closed and is enriched in isolated early phagosomes, extend from each membrane. SNARE proteins form indicating that focal exocytosis of VA M P3-related vesi- complexes that are required for membrane fusion. These cles is required for the onset of phagosome formation.16 complexes contain coiled-coil bundles consisting of four VA M P3 also mediates exocytosis of tumor necrosis helices, named for their conserved amino acid residues. factor alpha (TNF-α)-containing vesicles at the plasma Three of the helices (Qa-, Qb-, and Qc-SNARE motifs) membrane at the site of phagocytic cup formation with are extended from one membrane by proteins of the the yeast, Candida albicans.17 syntaxin (stx) and SNAP25 families that contain a Late endosome- or lysosome-localized VA M P7 conserved glutamine residue at a central position called (also called tetanus neurotoxin-insensitive VA M P the zero layer. The fourth helix (R-SNARE motif) is or TI-VA M P) is required for FcR- or complement extended from the opposite membrane by a protein of C3 receptor-mediated phagocytosis. Interestingly, as the vesicle-associated membrane protein (VA M P, also demonstrated by live-cell imaging experiments in called synaptobrevin) family that contains a conserved macrophages, VA M P7 recruitment to a phagosome arginine residue at the same position. Proper assembly follows VA M P3 recruitment to the same phagosome.18 of the SNAREs (Qa, Qbc, and R) leads to formation of However, in dendritic cells, VA M P7 and late endosome- the SNARE complex, resulting in membrane fusion and localized VA M P8 (also called endobrevin) are negative cargo delivery, and/or content mixing (Fig. 1).12–14 regulators of the phagocytosis of Escherichia coli.19 When foreign particles are recognized by specific Unfortunately, because green fluorescent protein GFP( ) receptors on the plasma membrane, the phagosome- is sensitive to the acidic pH of the phagosome, to use forming membrane is thought to originate not only E. coli expressing GFP for evaluation of phagocytosis from the invaginated plasma membrane, but also from efficiency is problematic. Knockdown of plasma mem- intracellular vesicles and/or organelles such as endo- brane-localized Qa-SNARE stx11 enhances the phago- somes and the endoplasmic reticulum (ER). Inhibition cytosis efficiency of primary human monocytes and 2 © 2020 Tottori University Medical Press Function and regulation of SNAP23 in phagocytosis Table 1. SNARE proteins that function during phagocytosis SNARE type SNARE protein Localization Function during phagocytosis Immune cells References Qa-SNARE syntaxin7 LE/LY phagosome maturation FcγRIIa-transfected 26 (promote) COS-1 cells, macrophages syntaxin11 PM phagosome formation macrophages 20, 21 (suppress or no involvement) syntaxin13 EE/RE phagosome maturation FcγRIIa-transfected 26 (promote) COS-1 cells, macrophages syntaxin18 ER phagosome formation macrophages 22 (promote) Qc-SNARE D12 (p31) ER phagosome formation macrophages 22 (promote) Qbc-SNARE SNAP23 PM phagosome formation and maturation macrophages, 10, 11 (dependent on phosphorylation) dendritic cells R-SNARE VA MP3 RE phagosome formation and maturation macrophages, 16, 18 (promote) dendritic cells VA MP7 LE/LY phagosome formation and maturation macrophages 18 (promote) VA MP8 LE/LY, RE phagosome
Load more

Recommended publications
  • Directed Proximity-Dependent Biotin Labelling in Zebrafish
    TOOLS AND RESOURCES In vivo proteomic mapping through GFP- directed proximity-dependent biotin labelling in zebrafish Zherui Xiong1, Harriet P Lo1, Kerrie-Ann McMahon1, Nick Martel1, Alun Jones1, Michelle M Hill2, Robert G Parton1,3*, Thomas E Hall1* 1Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; 2QIMR Berghofer Medical Research Institute, Herston, Australia; 3Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane, Australia Abstract Protein interaction networks are crucial for complex cellular processes. However, the elucidation of protein interactions occurring within highly specialised cells and tissues is challenging. Here, we describe the development, and application, of a new method for proximity- dependent biotin labelling in whole zebrafish. Using a conditionally stabilised GFP-binding nanobody to target a biotin ligase to GFP-labelled proteins of interest, we show tissue-specific proteomic profiling using existing GFP-tagged transgenic zebrafish lines. We demonstrate the applicability of this approach, termed BLITZ (Biotin Labelling In Tagged Zebrafish), in diverse cell types such as neurons and vascular endothelial cells. We applied this methodology to identify interactors of caveolar coat protein, cavins, in skeletal muscle. Using this system, we defined specific interaction networks within in vivo muscle cells for the closely related but functionally distinct Cavin4 and Cavin1 proteins. *For correspondence: Introduction [email protected] (RGP); [email protected] (TEH) The understanding of the biological functions of a protein requires detailed knowledge of the mole- cules with which it interacts. However, robust elucidation of interacting proteins, including not only Competing interests: The strong direct protein-protein interactions, but also weak, transient or indirect interactions is challeng- authors declare that no ing.
    [Show full text]
  • Protein Interaction Network of Alternatively Spliced Isoforms from Brain Links Genetic Risk Factors for Autism
    ARTICLE Received 24 Aug 2013 | Accepted 14 Mar 2014 | Published 11 Apr 2014 DOI: 10.1038/ncomms4650 OPEN Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism Roser Corominas1,*, Xinping Yang2,3,*, Guan Ning Lin1,*, Shuli Kang1,*, Yun Shen2,3, Lila Ghamsari2,3,w, Martin Broly2,3, Maria Rodriguez2,3, Stanley Tam2,3, Shelly A. Trigg2,3,w, Changyu Fan2,3, Song Yi2,3, Murat Tasan4, Irma Lemmens5, Xingyan Kuang6, Nan Zhao6, Dheeraj Malhotra7, Jacob J. Michaelson7,w, Vladimir Vacic8, Michael A. Calderwood2,3, Frederick P. Roth2,3,4, Jan Tavernier5, Steve Horvath9, Kourosh Salehi-Ashtiani2,3,w, Dmitry Korkin6, Jonathan Sebat7, David E. Hill2,3, Tong Hao2,3, Marc Vidal2,3 & Lilia M. Iakoucheva1 Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.
    [Show full text]
  • 5850.Full.Pdf
    Soluble NSF Attachment Protein Receptors (SNAREs) in RBL-2H3 Mast Cells: Functional Role of Syntaxin 4 in Exocytosis and Identification of a Vesicle-Associated This information is current as Membrane Protein 8-Containing Secretory of September 25, 2021. Compartment Fabienne Paumet, Joëlle Le Mao, Sophie Martin, Thierry Galli, Bernard David, Ulrich Blank and Michèle Roa Downloaded from J Immunol 2000; 164:5850-5857; ; doi: 10.4049/jimmunol.164.11.5850 http://www.jimmunol.org/content/164/11/5850 http://www.jimmunol.org/ References This article cites 60 articles, 36 of which you can access for free at: http://www.jimmunol.org/content/164/11/5850.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 25, 2021 • No Triage! Every submission reviewed by practicing scientists • 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 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 © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Soluble NSF Attachment Protein Receptors (SNAREs) in RBL-2H3 Mast Cells: Functional Role of Syntaxin 4 in Exocytosis and Identification of a Vesicle-Associated Membrane Protein 8-Containing Secretory Compartment1 Fabienne Paumet,* Joe¨lle Le Mao,* Sophie Martin,* Thierry Galli,† Bernard David,* Ulrich Blank,* and Miche`le Roa2* Mast cells upon stimulation through high affinity IgE receptors massively release inflammatory mediators by the fusion of spe- cialized secretory granules (related to lysosomes) with the plasma membrane.
    [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]
  • Supplementary Figures 1-14 and Supplementary References
    SUPPORTING INFORMATION Spatial Cross-Talk Between Oxidative Stress and DNA Replication in Human Fibroblasts Marko Radulovic,1,2 Noor O Baqader,1 Kai Stoeber,3† and Jasminka Godovac-Zimmermann1* 1Division of Medicine, University College London, Center for Nephrology, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK. 2Insitute of Oncology and Radiology, Pasterova 14, 11000 Belgrade, Serbia 3Research Department of Pathology and UCL Cancer Institute, Rockefeller Building, University College London, University Street, London WC1E 6JJ, UK †Present Address: Shionogi Europe, 33 Kingsway, Holborn, London WC2B 6UF, UK TABLE OF CONTENTS 1. Supplementary Figures 1-14 and Supplementary References. Figure S-1. Network and joint spatial razor plot for 18 enzymes of glycolysis and the pentose phosphate shunt. Figure S-2. Correlation of SILAC ratios between OXS and OAC for proteins assigned to the SAME class. Figure S-3. Overlap matrix (r = 1) for groups of CORUM complexes containing 19 proteins of the 49-set. Figure S-4. Joint spatial razor plots for the Nop56p complex and FIB-associated complex involved in ribosome biogenesis. Figure S-5. Analysis of the response of emerin nuclear envelope complexes to OXS and OAC. Figure S-6. Joint spatial razor plots for the CCT protein folding complex, ATP synthase and V-Type ATPase. Figure S-7. Joint spatial razor plots showing changes in subcellular abundance and compartmental distribution for proteins annotated by GO to nucleocytoplasmic transport (GO:0006913). Figure S-8. Joint spatial razor plots showing changes in subcellular abundance and compartmental distribution for proteins annotated to endocytosis (GO:0006897). Figure S-9. Joint spatial razor plots for 401-set proteins annotated by GO to small GTPase mediated signal transduction (GO:0007264) and/or GTPase activity (GO:0003924).
    [Show full text]
  • Uncoupling the Functions of CALM in VAMP Sorting and Clathrin-Coated Pit Formation
    Uncoupling the Functions of CALM in VAMP Sorting and Clathrin-Coated Pit Formation Daniela A. Sahlender¤a, Patrycja Kozik¤b, Sharon E. Miller, Andrew A. Peden¤c, Margaret S. Robinson* Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom Abstract CALM (clathrin assembly lymphoid myeloid leukemia protein) is a cargo-selective adaptor for the post-Golgi R-SNAREs VAMPs 2, 3, and 8, and it also regulates the size of clathrin-coated pits and vesicles at the plasma membrane. The present study has two objectives: to determine whether CALM can sort additional VAMPs, and to investigate whether VAMP sorting contributes to CALM-dependent vesicle size regulation. Using a flow cytometry-based endocytosis efficiency assay, we demonstrate that CALM is also able to sort VAMPs 4 and 7, even though they have sorting signals for other clathrin adaptors. CALM homologues are present in nearly every eukaryote, suggesting that the CALM family may have evolved as adaptors for retrieving all post-Golgi VAMPs from the plasma membrane. Using a knockdown/rescue system, we show that wild-type CALM restores normal VAMP sorting in CALM-depleted cells, but that two non-VAMP-binding mutants do not. However, when we assayed the effect of CALM depletion on coated pit morphology, using a fluorescence microscopy- based assay, we found that the two mutants were as effective as wild-type CALM. Thus, we can uncouple the sorting function of CALM from its structural role. Citation: Sahlender DA, Kozik P, Miller SE, Peden AA, Robinson MS (2013) Uncoupling the Functions of CALM in VAMP Sorting and Clathrin-Coated Pit Formation.
    [Show full text]
  • STX Stainless Steel Boxes Characteristics Enclosure and Door Manufactured from AISI 304 Stainless Steel (AISI 316 on Request)
    STX stainless steel boxes characteristics Enclosure and door manufactured from AISI 304 stainless steel (AISI 316 on request). Mounting plate manufactured from 2.5mm sendzimir sheet steel. Hinge in stainless steel. composition Box complete with: • mounting plate • locking system body in zinc alloy and lever in stainless steel with Ø 3mm double bar key • package with hardware for earth connection and screws to mounting plate. conformity and approval protection degree • IP 65 complying with EN50298; EN60529 for box with single blank door • IP 55 complying with EN50298; EN60529 for box with double blank door • type 12, 4, 4X complying with UL508A; UL50 • impact resistance IK10 complying with EN50298; EN50102. box with single blank door code B A P C D E F weight kg mod. art. STX2 315 200 300 150 150 250 * 219 6 STX3 415 300 400 150 250 350 215 319 9,5 STX3 420 300 400 200 250 350 215 319 11 STX4 315 400 300 150 350 250 315 219 9,5 STX4 420 400 400 200 350 350 315 319 13,5 STX4 520 400 500 200 350 450 315 419 15,5 STX4 620 400 600 200 350 550 315 519 18 STX5 520 500 500 200 450 450 415 419 18 STX5 725 500 700 250 450 650 415 619 27 STX6 420 600 400 200 550 350 315 519 17,3 STX6 620 600 600 200 550 550 515 519 24,5 STX6 625 600 600 250 550 550 515 519 27 STX6 630 600 600 300 550 550 515 519 30 STX6 820 600 800 200 550 750 515 719 31 STX6 825 600 800 250 550 750 515 719 34 STX6 830 600 800 300 550 750 515 719 37 STX6 1230 600 1200 300 550 1150 515 1119 54 STX8 830 800 800 300 750 750 715 719 48 STX8 1030 800 1000 300 750 950 715 919 58 STX8 1230 800 1200 300 750 1150 715 1119 67 * B=200 M6 studs welded only on the hinge side.
    [Show full text]
  • Fluorescence Lifetime Imaging Microscopy Reveals Rerouting Of
    RESEARCH ARTICLE Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation Danie¨ lle Rianne Jose´ Verboogen, Natalia Gonza´ lez Mancha, Martin ter Beest, Geert van den Bogaart* Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands Abstract SNARE proteins play a crucial role in intracellular trafficking by catalyzing membrane fusion, but assigning SNAREs to specific intracellular transport routes is challenging with current techniques. We developed a novel Fo¨ rster resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM)-based technique allowing visualization of real-time local interactions of fluorescently tagged SNARE proteins in live cells. We used FRET-FLIM to delineate the trafficking steps underlying the release of the inflammatory cytokine interleukin-6 (IL-6) from human blood- derived dendritic cells. We found that activation of dendritic cells by bacterial lipopolysaccharide leads to increased FRET of fluorescently labeled syntaxin 4 with VAMP3 specifically at the plasma membrane, indicating increased SNARE complex formation, whereas FRET with other tested SNAREs was unaltered. Our results revealed that SNARE complexing is a key regulatory step for cytokine production by immune cells and prove the applicability of FRET-FLIM for visualizing SNARE complexes in live cells with subcellular spatial resolution. DOI: 10.7554/eLife.23525.001 *For correspondence: geert. [email protected] Introduction Competing interests: The One of the central paradigms in cell biology is that all intracellular membrane fusion, except for authors declare that no mitochondrial fusion, is catalyzed by soluble NSF (N-ethylmaleimide-sensitive fusion protein) attach- competing interests exist. ment protein receptor (SNARE) proteins (Hong, 2005; Jahn and Scheller, 2006).
    [Show full text]
  • ST Brochure LR
    ST•STX SERIES The most intelligent sound reinforcement system Working together, there’s no problem we can’t solve, no schedule we can’t meet, no project on the planet. we can’t take to a higher level of excellence, from the White House to the Olympic SuperDome, from corner churches to major metropolitan concert halls. Much as we love technology, our greatest satisfaction comes through helping people communicate through music, dance, theater, or the power of a new idea brilliantly expressed. When we make those kinds of connections, there’s nothing more exciting – or more powerful. Here are some of the unique technologies we use to help people communicate: Patented CoEntrant Topology integrates System Specific Electronics integrate pre- midrange and high frequency drivers into configured signal processing and protection wideband point sources. with high performance amplifiers. Complex Conic Topology, the first new The R-Control Remote System Supervision approach to horn design in decades, has Network is based on Echelon’s LonWorks® proven its superior performance worldwide. protocol (ANSI/EIA 709.1). TRAP (TRue Array Principle) design PowerNet Series loudspeakers incorporate aligns acoustic centers so loudspeaker System Specific Electronics and can be clusters produce coherent output. upgraded for R-Control remote operation. Reference Point Array engineering optimizes EASE, EASE JR and EARS are the industry the entire signal chain from line level to standard modeling programs for acoustic listener for unprecedented performance. environments and sound system performance. CobraNet routes 64 channels of 20-bit digital audio over CAT 5 copper or UTP optical fiber using Ethernet protocols For more information on the latest integrated sound reinforcement innovations from R-H Engineering, visit us on our website.
    [Show full text]
  • Transcriptional Recapitulation and Subversion Of
    Open Access Research2007KaiseretVolume al. 8, Issue 7, Article R131 Transcriptional recapitulation and subversion of embryonic colon comment development by mouse colon tumor models and human colon cancer Sergio Kaiser¤*, Young-Kyu Park¤†, Jeffrey L Franklin†, Richard B Halberg‡, Ming Yu§, Walter J Jessen*, Johannes Freudenberg*, Xiaodi Chen‡, Kevin Haigis¶, Anil G Jegga*, Sue Kong*, Bhuvaneswari Sakthivel*, Huan Xu*, Timothy Reichling¥, Mohammad Azhar#, Gregory P Boivin**, reviews Reade B Roberts§, Anika C Bissahoyo§, Fausto Gonzales††, Greg C Bloom††, Steven Eschrich††, Scott L Carter‡‡, Jeremy E Aronow*, John Kleimeyer*, Michael Kleimeyer*, Vivek Ramaswamy*, Stephen H Settle†, Braden Boone†, Shawn Levy†, Jonathan M Graff§§, Thomas Doetschman#, Joanna Groden¥, William F Dove‡, David W Threadgill§, Timothy J Yeatman††, reports Robert J Coffey Jr† and Bruce J Aronow* Addresses: *Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. †Departments of Medicine, and Cell and Developmental Biology, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232, USA. ‡McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA. §Department of Genetics and Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. ¶Molecular Pathology Unit and Center for Cancer Research, Massachusetts deposited research General Hospital, Charlestown, MA 02129, USA. ¥Division of Human Cancer Genetics, The Ohio State University College of Medicine, Columbus, Ohio 43210-2207, USA. #Institute for Collaborative BioResearch, University of Arizona, Tucson, AZ 85721-0036, USA. **University of Cincinnati, Department of Pathology and Laboratory Medicine, Cincinnati, OH 45267, USA. ††H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. ‡‡Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology (CHIP@HST), Harvard Medical School, Boston, Massachusetts 02115, USA.
    [Show full text]
  • Species Groups Distributed Across Elevational Gradients Reveal Convergent and Continuous Genetic Adaptation to High Elevations
    Species groups distributed across elevational gradients reveal convergent and continuous genetic adaptation to high elevations Yan-Bo Suna,1, Ting-Ting Fua,b,1, Jie-Qiong Jina, Robert W. Murphya,c, David M. Hillisd,2, Ya-Ping Zhanga,e,f,2, and Jing Chea,e,g,2 aState Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 650223 Kunming, China; bKunming College of Life Science, University of Chinese Academy of Sciences, 650204 Kunming, China; cCentre for Biodiversity and Conservation Biology, Royal Ontario Museum, Toronto, ON M5S 2C6, Canada; dDepartment of Integrative Biology and Biodiversity Center, University of Texas at Austin, Austin, TX 78712; eCenter for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, 650223 Kunming, China; fState Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, 650091 Kunming, China; and gSoutheast Asia Biodiversity Research Institute, Chinese Academy of Sciences, Yezin, 05282 Nay Pyi Taw, Myanmar Contributed by David M. Hillis, September 7, 2018 (sent for review August 7, 2018; reviewed by John H. Malone and Fuwen Wei) Although many cases of genetic adaptations to high elevations Most previous studies of the genetic processes of HEA have have been reported, the processes driving these modifications and compared species or populations from high elevations above the pace of their evolution remain unclear. Many high-elevation 3,500 m with those from low elevations to identify sequence adaptations (HEAs) are thought to have arisen in situ as popula- variation and/or expression shifts in the high-elevation group (8– tions rose with growing mountains.
    [Show full text]
  • Post-Transcriptionally Impaired De Novo Mutations Contribute to The
    bioRxiv preprint doi: https://doi.org/10.1101/175844; this version posted November 26, 2019. 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. 1 Post-transcriptionally impaired de novo mutations 2 contribute to the genetic etiology of four neuropsychiatric 3 disorders 4 5 Fengbiao Mao1,2¶, Lu Wang3¶, Xiaolu Zhao2, Zhongshan Li4, Luoyuan Xiao5, 6 Rajesh C. Rao2, Jinchen Li4, Huajing Teng1*, Xin He6*, and Zhong Sheng Sun1,4* 7 8 1 Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, 9 China. 10 2 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. 11 3 Institute of Life Science, Southeast University, Nanjing 210096, China. 12 4 Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325027, 13 China 14 5 Department of Computer Science and Technology, Tsinghua University, Beijing 15 100084, China. 16 6 Department of Human Genetics, University of Chicago, Chicago, IL, USA. 17 18 ¶These authors contributed equally to this work 19 * Corresponding authors 20 E-mail: 21 [email protected] (Z.S.S.) 22 [email protected] (X.H.) 23 [email protected] (H.T.) 24 25 1 bioRxiv preprint doi: https://doi.org/10.1101/175844; this version posted November 26, 2019. 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.
    [Show full text]