Dissecting Mechanisms Controlling Neural Network Formation in Drosophila Melanogaster
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Neuregulin-1 Potentiates Agrin-Induced Acetylcholine Receptor Clustering Through Muscle-Specific Kinase Phosphorylation
Research Article 1531 Neuregulin-1 potentiates agrin-induced acetylcholine receptor clustering through muscle-specific kinase phosphorylation Shyuan T. Ngo1, Rebecca N. Cole3, Nana Sunn2, William D. Phillips3,* and Peter G. Noakes1,2,*,` 1School of Biomedical Sciences, University of Queensland, St. Lucia, 4072, Queensland, Australia 2Queensland Brain Institute, University of Queensland, St. Lucia, 4072, Queensland, Australia 3Physiology and Bosch Institute, The University of Sydney, New South Wales, 2006, Australia *These authors contributed equally to this work `Author for correspondence ([email protected]) Accepted 14 November 2011 Journal of Cell Science 125, 1531–1543 ß 2012. Published by The Company of Biologists Ltd doi: 10.1242/jcs.095109 Summary At neuromuscular synapses, neural agrin (n-agrin) stabilizes embryonic postsynaptic acetylcholine receptor (AChR) clusters by signalling through the muscle-specific kinase (MuSK) complex. Live imaging of cultured myotubes showed that the formation and disassembly of primitive AChR clusters is a dynamic and reversible process favoured by n-agrin, and possibly other synaptic signals. Neuregulin-1 is a growth factor that can act through muscle ErbB receptor kinases to enhance synaptic gene transcription. Recent studies suggest that neuregulin-1–ErbB signalling can modulate n-agrin-induced AChR clustering independently of its effects on transcription. Here we report that neuregulin-1 increased the size of developing AChR clusters when injected into muscles of embryonic mice. We investigated this phenomenon using cultured myotubes, and found that in the ongoing presence of n-agrin, neuregulin-1 potentiates AChR clustering by increasing the tyrosine phosphorylation of MuSK. This potentiation could be blocked by inhibiting Shp2, a postsynaptic tyrosine phosphatase known to modulate the activity of MuSK. -
Induction of Myasthenia by Immunization Against Muscle- Specific Kinase
Induction of myasthenia by immunization against muscle- specific kinase Kazuhiro Shigemoto, … , Norifumi Ueda,, Seiji Matsuda J Clin Invest. 2006;116(4):1016-1024. https://doi.org/10.1172/JCI21545. Research Article Autoimmunity Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChRs) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJs). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJs. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG. Find the latest version: https://jci.me/21545/pdf Research article Induction of myasthenia by immunization against muscle-specific kinase Kazuhiro Shigemoto,1,2 Sachiho Kubo,2 Naoki Maruyama,2 Naohito Hato,3 Hiroyuki Yamada,3 Chen Jie,4 Naoto Kobayashi,4 Katsumi Mominoki,5 Yasuhito Abe,6 Norifumi Ueda,6 and Seiji Matsuda4 1Department of Preventive Medicine, Ehime University School of Medicine, Ehime, Japan. 2Department of Molecular Pathology, Tokyo Metropolitan Institute for Gerontology, Tokyo, Japan. 3Department of Otolaryngology and 4Department of Integrated Basic Medical Science, Ehime University School of Medicine, Ehime, Japan. -
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1 Exploring the male-induced female reproduction of Schistosoma mansoni in a novel medium Jipeng Wang1, Rui Chen1, James Collins1 1) UT Southwestern Medical Center. Schistosomiasis is a neglected tropical disease caused by schistosome parasites that infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs, yet our understanding of their sexual reproduction is limited because egg production is not sustained for more than a few days in vitro. Here, we explore the process of male-stimulated female maturation in our newly developed ABC169 medium and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. By performing an RNAi screen for genes whose expression was enriched in the female reproductive organs, we identify a single nuclear hormone receptor that is required for differentiation and maturation of germ line stem cells in female gonad. Furthermore, we screen genes in non-reproductive tissues that maybe involved in mediating cell signaling during the male-female interplay and identify a transcription factor gli1 whose knockdown prevents male worms from inducing the female sexual maturation while having no effect on male:female pairing. Using RNA-seq, we characterize the gene expression changes of male worms after gli1 knockdown as well as the female transcriptomic changes after pairing with gli1-knockdown males. We are currently exploring the downstream genes of this transcription factor that may mediate the male stimulus associated with pairing. -
(12) United States Patent (10) Patent N0.: US 7,267,820 B2 Vincent Et A]
US007267820B2 (12) United States Patent (10) Patent N0.: US 7,267,820 B2 Vincent et a]. (45) Date of Patent: Sep. 11,2007 (54) NEUROTRANSMISSION DISORDERS Glass, D]. et a1. Agrin acts via a MuSK receptor complex. Cell. May 17, 1996;85(4):513-23. (75) Inventors: Angela Vincent, Oxford (GB); Werner Hoch W, et al., Auto-antibodies to the receptor tyrosine kinase Hoch, Houston, TX (US) MuSK in patients with myasthenia gravis without acetycholine receptor antibodies. Nat Med. Mar. 2001;7(3):365-8. (73) Assignees: Isis Innovation Limited, Oxford (GB); Hoch, W., et a1. Structural domains of agrin required for clustering of nicotinic acetylcholine receptors. EMBO J. Jun. 15, Max-Planck Gesellschaft zur 1994;13(12):2814-21. Foerderung der Wissenschaften e.V., Hopf. C., Hoch, W. Heparin inhibits acetycholine receptor-aggre Munich (DE) gation at two distinct steps in the agrin-induced pathway. Eur J Neurosci. Jun. 1997;9(6):1170-7. ( * ) Notice: Subject to any disclaimer, the term of this Hopf, C., Hoch, W. DimeriZation of the muscle-speci?c kinase patent is extended or adjusted under 35 induces tyrosine phosphorylation of acetycholine receptors and their U.S.C. 154(b) by 506 days. aggregation on the surface of myotubes. J Biol Chem. Mar. 13, 1998;273(11):6467-73. (21) Appl. No.: 10/311,575 Hopf, C., Hoch, W. Tyrosine phosphorylation of the muscle-speci?c kinase is exclusively induced by acetycholine receptor-aggregating (22) PCT Filed: Jun. 15, 2001 agrin fragments. Eur JBiochem. Apr. 15, 1998;253(2):382-9. Lindstrom, J ., Seybold,.M.E., Lennon, V.A., Whittingham, S., (86) PCT N0.: PCT/GB01/02661 Duane, D.D., Antibody to acetycholine receptor in myasthenia gravis. -
Proquest Dissertations
L-type calcium channels mediate nicotinic acetylcholine receptor aggregation on cultured myotubes Item Type text; Dissertation-Reproduction (electronic) Authors Milholland, Rebecca Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 06/10/2021 03:16:03 Link to Item http://hdl.handle.net/10150/280370 L-TYPE CALCIUM CHANNELS MEDIATE NICOTINIC ACETYLCHOLINE RECEPTOR AGGREGATION ON CULTURED MYOTUBES by Rebecca B. R. Milholland Copyright © Rebecca B. R. Milholland 2 0 0 3 A Dissertation Subnnitted to the Faculty of the GRADUATE INTERDISCIPLINARY PROGRAM IN PHARMACOLOGY AND TOXICOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate college THE UNIVERSITY OF ARIZONA 2003 UMI Number: 3107021 Copyright 2003 by IVIilholland, Rebecca Bliss Ryan All rights reserved. UMI UMI Microform 3107021 Copyright 2004 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 •7 THE UNIVERSITY OF ARIZONA ® GRADUATE COLLEGE As members of the Final Examination Committee, we certify that we have read the dissertation prepared by Rebecca B. R. Milholland entitled L-Type Calcium Channels Mediate AChR Aggregation on Cultured Myotubes and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy /nai/18 ndrea Date Herman Gordon Date Pk Jj-- yL^ aul St.John ~ 7 Daa tie I I Daniel Stamer Date tCpJ Ro kas Date Final approval and acceptance of this dissertation is contingent upon the candidate's submission of the final copy of the dissertation to the Graduate College. -
13Th YSA Phd Symposium 2017 Book of Abstracts: Poster Presentations
13th YSA PhD Symposium 2017 Book of Abstracts: Poster Presentations P 1 Efficient Subject Independent BCI based on Local Temporal Correlation Common Spatial Pattern method Hatamikia, S. (1)*, Nasrabadi, AM. (2) 1-university of Islamic Azad, Science and Research branch, Tehran, Iran,2-Center for Biomedical Engineering and Physics, Medical University Vienna, Austria, university of Shahed University Tehran, Iran [email protected] One of the main weaknesses of the proposed EEG-based Brain Computer interfaces (BCIs) is the requirement for specific subject training data to train a classifier. Almost all proposed BCIs in literature are custom-designed and dedicated to just one particular subject. Eliminating the calibration phase can be regarded as a good solution to enable new users to have an immediate interaction with BCIs. In addition, eliminating calibration training sessions has a vital role for those patients who have visual and audible deficiencies. Such patients do not have the mental or physical ability to perform training sessions needed for the subject dependent BCIs implementation. This study presents an efficient subject-independent approach for BCIs based on EEG signals. The main goal of this study is to develop ready-to-use motor imagery tasks based BCIs using other subjects' data, which can be utilizable for anyone, who is shown the system for the first time. To achieve this approach, we proposed a subject-independent method based on Local Temporal Correlation Common Spatial Pattern (LTCCSP) algorithm for feature selection and Genetic algorithm (GA) strategy, using Frobenious distance index, to have a simultaneous optimization of time interval and frequency. In this study, publicly available dataset IVa of the BCI competition III is used. -
Muscle-Specific Receptor Tyrosine Kinase Endocytosis in Acetylcholine Receptor Clustering in Response to Agrin
1688 • The Journal of Neuroscience, February 13, 2008 • 28(7):1688–1696 Cellular/Molecular Muscle-Specific Receptor Tyrosine Kinase Endocytosis in Acetylcholine Receptor Clustering in Response to Agrin Dan Zhu,1 Zhihua Yang,1 Zhenge Luo,2 Shiwen Luo,1 Wen C. Xiong,1 and Lin Mei1 1Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, and 2Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Scineces, Chinese Academy of Sciences, Shanghai 200031, China Agrin, a factor used by motoneurons to direct acetylcholine receptor (AChR) clustering at the neuromuscular junction, initiates signal transduction by activating the muscle-specific receptor tyrosine kinase (MuSK). However, the underlying mechanisms remain poorly defined. Here, we demonstrated that MuSK became rapidly internalized in response to agrin, which appeared to be required for induced AChR clustering. Moreover, we provided evidence for a role of N-ethylmaleimide sensitive factor (NSF) in regulating MuSK endocytosis and subsequent signaling in response to agrin stimulation. NSF interacts directly with MuSK with nanomolar affinity, and treatment of muscle cells with the NSF inhibitor N-ethylmaleimide, mutation of NSF, or suppression of NSF expression all inhibited agrin-induced AChR clustering. Furthermore, suppression of NSF expression and NSF mutation attenuate MuSK downstream signaling. Our study reveals a potentially novel mechanism that regulates agrin/MuSK signaling cascade. Key words: neuromuscular junction; nicotinic acetylcholine receptors; agrin; endocytosis; MuSK; NSF Introduction dependent manner (Okada et al., 2006; Jones et al., 2007). Agrin/ The vertebrate neuromuscular junction (NMJ) is a synapse MuSK signaling is mediated or regulated by several interacting formed between motoneurons and skeletal muscle fibers. -
(12) United States Patent (10) Patent No.: US 8,034,913 B2 Hunt Et Al
USOO8034913B2 (12) United States Patent (10) Patent No.: US 8,034,913 B2 Hunt et al. (45) Date of Patent: Oct. 11, 2011 (54) RECOMBINANTLY MODIFIED PLASMIN FOREIGN PATENT DOCUMENTS CA 2045869 12/1991 (75) Inventors: Jennifer A. Hunt, Raleigh, NC (US); WO WO 97.27331 A2 7/1997 Valery Novokhatny, Raleigh, NC (US) WO WO99,05322 A1 2/1999 WO WOO1,9436.6 A1 12/2001 WO WOO2,5O290 A1 6, 2002 (73) Assignee: Grifols Therapeutics Inc., Research WO WOO3/O54232 A2 7, 2003 Triangle Park, NC (US) WO WO 2004/052228 A2 6, 2004 WO WO 2005,105990 11, 2005 WO WO 2007/047874 4/2007 (*) Notice: Subject to any disclaimer, the term of this WO WO 2009,0734.71 6, 2009 patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 854 days. Hunt et al. Simplified recombinant plasmin: Production and func tional comparison of a novel thrombolytic molecule with plasma (21) Appl. No.: 11/568,023 derived plasmin. Thromb. Haemost 100:413-419, 2008.* Andrianov, S.I., et al., “Peculiarities of Hydrolytic Action of Plasmin, (22) PCT Filed: Apr. 21, 2005 Miniplasmin, Microplasmin and Trypsin on Polymeric Fibrin.” Ukr. Biokhim. Zh., 64(3): 14-20 (1992). Anonick, P. et al., “Regulation of Plasmin, Miniplasmin and (86). PCT No.: PCT/US2OOS/O13562 Streptokinase-Plasmin Complex by-O.--Antiplasmin, O.-- S371 (c)(1) Macroglobulin, and Antithrombin III in the Presence of Heparin.” . Thrombosis Res., 59: 449-462 (1990). (2), (4) Date: Feb. 1, 2008 Bennett, D., et al., “Kinetic Characterization of the Interaction of Biotinylated Human Interleukin 5 with an Fc Chimera of its Receptor (87) PCT Pub. -
Cloning of Receptor Tyrosine Kinases from Anvsia
Cloning of Receptor Tyrosine Kinases From ANvsia Jonathan Hislop Neurology and Neurosurgery, McGill University, Montreal. August, 1998 A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements of the degree of Master of Science @Jonathan Hislop, 1998 National Library Biblioth$ue nationale du Cana a Acquisitions and Acquisitions et Bibbgraphic Semices m~icesbibliographiques 395 Wdlngton Street 395, rue Weilinglori OItawaON K1AW OnawaON K1AON4 CariPds Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence ailowing the exclusive permettant a la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or seU reproduire, prêter, distribuer ou copies of this thesis in rnicrofonn, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/film, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substaatial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or othenirise de celle-ci ne doivent être imprimes reproduced without the author's ou autrement reproduits sans son permission. autorisation. Abstract I have cloned two putative receptor tyrosine kinases (RTKs) fiom Aplysia californica, designated Aror and Anif. Aror is homologous to RTKs fiom the Ror subfarnily. Furthemore, Aror contains an extracellular immunoglobulin-like domain, cysteine-rich region, and kringie domain. These domains are d characteristic of Ror recepton. Amf is homologous to members of the Ret and FGF receptor subfamilies of RTKs. -
The Molecular Basis of Blood Coagulation Review
Cell, Vol. 53, 505-518, May 20, 1988, Copyright 0 1988 by Cell Press The Molecular Basis Review of Blood Coagulation Bruce Furie and Barbara C. Furie into the fibrin polymer. The clot, formed after tissue injury, Center for Hemostasis and Thrombosis Research is composed of activated platelets and fibrin. The clot Division of Hematology/Oncology mechanically impedes the flow of blood from the injured Departments of Medicine and Biochemistry vessel and minimizes blood loss from the wound. Once a New England Medical Center stable clot has formed, wound healing ensues. The clot is and Tufts University School of Medicine gradually dissolved by enzymes of the fibrinolytic system. Boston, Massachusetts 02111 Blood coagulation may be initiated through either the in- trinsic pathway, where all of the protein components are present in blood, or the extrinsic pathway, where the cell- Overview membrane protein tissue factor plays a critical role. Initia- tion of the intrinsic pathway of blood coagulation involves Blood coagulation is a host defense system that assists in the activation of factor XII to factor Xlla (see Figure lA), maintaining the integrity of the closed, high-pressure a reaction that is promoted by certain surfaces such as mammalian circulatory system after blood vessel injury. glass or collagen. Although kallikrein is capable of factor After initiation of clotting, the sequential activation of cer- XII activation, the particular protease involved in factor XII tain plasma proenzymes to their enzyme forms proceeds activation physiologically is unknown. The collagen that through either the intrinsic or extrinsic pathway of blood becomes exposed in the subendothelium after vessel coagulation (Figure 1A) (Davie and Fiatnoff, 1964; Mac- damage may provide the negatively charged surface re- Farlane, 1964). -
Differential Binding of Plasminogen, Plasmin, and Angiostatin4.5 to Cell Surface B-Actin: Implications for Cancer-Mediated Angiogenesis
Research Article Differential Binding of Plasminogen, Plasmin, and Angiostatin4.5 to Cell Surface B-Actin: Implications for Cancer-Mediated Angiogenesis Hao Wang,1 Jennifer A. Doll,1 Keyi Jiang,1 Deborah L. Cundiff,1 Jarema S. Czarnecki,1 Mindy Wilson,2 Karen M. Ridge,2 and Gerald A. Soff1,3 1Division of Hematology/Oncology and 2Division of Pulmonary and Critical Care Medicine, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois and 3Division of Hematology/ Oncology, State University of New York Downstate Medical Center, Brooklyn, New York Abstract Several angiostatin isoforms have been reported, differing in Angiostatin4.5 (AS4.5) is the product of plasmin autoproteol- kringle content. Angiostatins consisting of plasminogen kringles 1 f to 3, kringles 1 to 4, or angiostatin4.5 (AS4.5), which includes ysis and consists of kringles 1 to 4 and 85% of kringle 5. In 78 529 culture, cancer cell surface globular B-actin mediates plasmin kringles 1 to 4 plus 85% of kringle 5 (Lys -Arg ), have been autoproteolysis to AS4.5. We now show that plasminogen generated in vitro by a variety of proteinases. However, it is still not binds to prostate cancer cells and that the binding colocalizes well understood which angiostatin isoforms are present naturally with surface B-actin, but AS4.5 does not bind to the cell in the human body (5, 8–13). We have shown previously that surface. Plasminogen and plasmin bind to immobilized AS4.5 is a naturally occurring human form (14). AS4.5 is generated B-actin similarly, with a K of f140 nmol/L. -
Supplementary Materials
Supplementary Materials 0.3 0.274 0.28 0.2735 0.26 0.273 0.24 0.2725 0.22 0.2 0.272 ccTM−score 0.18 0.2715 0.16 0.271 0.14 0.2705 0.12 0.1 0.27 1 2 3 4 5 6 7 8 9 10 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 d gap penalty cut Figure S1. Selection of the optimal values for dcut and gap penalty. The experiments were done on 50% randomly selected groups from the SABmark_twi dataset. The gap penalty on the left panel is 0 and the dcut on the right panel is 4. 1 0.9 0.8 PCC=0.94 0.7 0.6 0.5 0.4 ACC of the MSTA 0.3 0.2 0.1 0 0 0.2 0.4 0.6 0.8 1 ACC of the PSA Figure S2. The correlation between the accuracy of the PSA and the MSTA. The data used in this figure are available in Table S5. Table S1. The influence of TM-score normalization. TM-score_s/TM-score_b is the mean TM-score normalized by the size of the smaller/bigger protein. ccTM-score_s and ccTM-score_b are the mean common core TM-scores of the corresponding MSTA. Dataset HOMSTRAD SABmark_sup SABmark_twi SISY-multiple Number of groups 398 425 209 86 Mean length difference 17.5 34.1 43.4 65.2 Pairwise TM-score_s 0.810 0.683 0.575 0.692 Pairwise TM-score_b 0.756 0.597 0.476 0.571 No.