Association of Common Copy Number Variants at the Glutathione S
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Dynamin Functions and Ligands: Classical Mechanisms Behind
1521-0111/91/2/123–134$25.00 http://dx.doi.org/10.1124/mol.116.105064 MOLECULAR PHARMACOLOGY Mol Pharmacol 91:123–134, February 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics MINIREVIEW Dynamin Functions and Ligands: Classical Mechanisms Behind Mahaveer Singh, Hemant R. Jadhav, and Tanya Bhatt Department of Pharmacy, Birla Institute of Technology and Sciences Pilani, Pilani Campus, Rajasthan, India Received May 5, 2016; accepted November 17, 2016 Downloaded from ABSTRACT Dynamin is a GTPase that plays a vital role in clathrin-dependent pathophysiology of various disorders, such as Alzheimer’s disease, endocytosis and other vesicular trafficking processes by acting Parkinson’s disease, Huntington’s disease, Charcot-Marie-Tooth as a pair of molecular scissors for newly formed vesicles originating disease, heart failure, schizophrenia, epilepsy, cancer, dominant ’ from the plasma membrane. Dynamins and related proteins are optic atrophy, osteoporosis, and Down s syndrome. This review is molpharm.aspetjournals.org important components for the cleavage of clathrin-coated vesicles, an attempt to illustrate the dynamin-related mechanisms involved phagosomes, and mitochondria. These proteins help in organelle in the above-mentioned disorders and to help medicinal chemists division, viral resistance, and mitochondrial fusion/fission. Dys- to design novel dynamin ligands, which could be useful in the function and mutations in dynamin have been implicated in the treatment of dynamin-related disorders. Introduction GTP hydrolysis–dependent conformational change of GTPase dynamin assists in membrane fission, leading to the generation Dynamins were originally discovered in the brain and identi- of endocytic vesicles (Praefcke and McMahon, 2004; Ferguson at ASPET Journals on September 23, 2021 fied as microtubule binding partners. -
Solitary and Repetitive Binding Motifs for the Ap2 Complex Α-Appendage in Amphiphysin and Other Accessory Proteins
SOLITARY AND REPETITIVE BINDING MOTIFS FOR THE AP2 COMPLEX α-APPENDAGE IN AMPHIPHYSIN AND OTHER ACCESSORY PROTEINS Lene E. Olesen*, Eva M. Schmid*, Marijn G. J. Ford#*, Yvonne Vallis, M. Madan Babu, Peter Li, Ian G. Mills∑, Harvey T. McMahon§ and Gerrit J.K. Praefcke♣§ Laboratory of Molecular Biology, Medical Research Council, Neurobiology Division, Hills Road, Cambridge CB2 2QH, UK. ♣ Center for Molecular Medicine Cologne (CMMC), Institute for Genetics, Zülpicher Straße 47, 50674 Köln, Germany. Running Title: Classification of AP2 α-appendage-binding FxDxF and DxF/W motifs § Address correspondence to: Harvey T. McMahon, Email: [email protected]; Tel.: +44(0)1223-402311; Fax: +44(0)1223-402310 or Gerrit J.K. Praefcke, Email [email protected]; Tel.: +49(0)221-470-1561; Fax: +49(0)221-470-6749 Adaptor protein (AP) complexes bind to coated pits, for the platform subdomain of the transmembrane proteins destined for α-appendage. The motif domain of internalisation and to membrane lipids, so amphiphysin1 contains one copy of each of a linking cargo to the accessory internalisation DxF/W and FxDxF motif. We find that the machinery. This machinery interacts with the FxDxF motif is the main determinant for the appendage domains of APs, which have high affinity interaction with the α-adaptin platform and β-sandwich subdomains, appendage. We describe the optimal sequence forming the binding surfaces for interacting of the FxDxF motif using thermodynamic and proteins. Proteins which interact with the structural data and show how sequence subdomains do so via short motifs, usually variation controls the affinities of these motifs found in regions of low structural complexity for the α-appendage. -
BIN1/M-Amphiphysin2 Induces Clustering of Phosphoinositides to Recruit Its Downstream Partner Dynamin
ARTICLE Received 19 May 2014 | Accepted 22 Oct 2014 | Published 9 Dec 2014 DOI: 10.1038/ncomms6647 BIN1/M-Amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin Laura Picas1, Julien Viaud2, Kristine Schauer1, Stefano Vanni3, Karim Hnia4, Vincent Fraisier5, Aure´lien Roux6, Patricia Bassereau7,Fre´de´rique Gaits-Iacovoni2, Bernard Payrastre2, Jocelyn Laporte4, Jean-Baptiste Manneville1 & Bruno Goud1 Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and fre- quently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its down- stream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumu- lation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins. 1 Institut Curie and CNRS UMR 144, 26 rue d’Ulm, 75005 Paris, France. 2 INSERM, UMR1048, Universite´ Toulouse III, Institut des Maladies Me´taboliques et Cardiovasculaires, 1 avenue Jean Poulhe`s, 31432 Toulouse, France. -
Genome-Wide Analysis of Host-Chromosome Binding Sites For
Lu et al. Virology Journal 2010, 7:262 http://www.virologyj.com/content/7/1/262 RESEARCH Open Access Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) Fang Lu1, Priyankara Wikramasinghe1, Julie Norseen1,2, Kevin Tsai1, Pu Wang1, Louise Showe1, Ramana V Davuluri1, Paul M Lieberman1* Abstract The Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP), regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP) combined with massively parallel deep-sequencing (ChIP-Seq) was used to identify cellular sites bound by EBNA1. Sites identified by ChIP- Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A con- sensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, sug- gesting that some of these sites are indirectly bound by EBNA1. -
Differential Physiological Role of BIN1 Isoforms in Skeletal Muscle Development, Function and Regeneration
bioRxiv preprint doi: https://doi.org/10.1101/477950; this version posted December 11, 2018. 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 4.0 International license. Differential physiological role of BIN1 isoforms in skeletal muscle development, function and regeneration Ivana Prokic1,2,3,4, Belinda Cowling1,2,3,4, Candice Kutchukian5, Christine Kretz1,2,3,4, Hichem Tasfaout1,2,3,4, Josiane Hergueux1,2,3,4, Olivia Wendling1,2,3,4, Arnaud Ferry10, Anne Toussaint1,2,3,4, Christos Gavriilidis1,2,3,4, Vasugi Nattarayan1,2,3,4, Catherine Koch1,2,3,4, Jeanne Lainné6,7, Roy Combe2,3,4,8, Laurent Tiret9, Vincent Jacquemond5, Fanny Pilot-Storck9, Jocelyn Laporte1,2,3,4 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France 2Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, France 3Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Illkirch, France 4Université de Strasbourg, Illkirch, France 5Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR-5310, INSERM U-1217, Institut NeuroMyoGène, 8 avenue Rockefeller, 69373 Lyon, France 6Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 974, F- 75013, Paris, France 7Sorbonne Université, Department of Physiology, UPMC Univ Paris 06, Pitié-Salpêtrière Hospital, F- 75013, Paris, France 8CELPHEDIA-PHENOMIN, Institut Clinique de la Souris (ICS), Illkirch, France 9U955 – IMRB, Team 10 - Biology of the neuromuscular system, Inserm, UPEC, Ecole nationale vétérinaire d’Alfort, Maisons-Alfort, 94700, France 10Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 794, F- 75013, Paris, France Correspondence to: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/477950; this version posted December 11, 2018. -
REPORT Germline Mutation of INI1/SMARCB1 in Familial Schwannomatosis
REPORT Germline Mutation of INI1/SMARCB1 in Familial Schwannomatosis Theo J. M. Hulsebos, Astrid S. Plomp, Ruud A. Wolterman, Els C. Robanus-Maandag, Frank Baas, and Pieter Wesseling Patients with schwannomatosis develop multiple schwannomas but no vestibular schwannomas diagnostic of neurofi- bromatosis type 2. We report an inactivating germline mutation in exon 1 of the tumor-suppressor gene INI1 in a father and daughter who both had schwannomatosis. Inactivation of the wild-type INI1 allele, by a second mutation in exon 5 or by clear loss, was found in two of four investigated schwannomas from these patients. All four schwannomas displayed complete loss of nuclear INI1 protein expression in part of the cells. Although the exact oncogenetic mechanism in these schwannomas remains to be elucidated, our findings suggest that INI1 is the predisposing gene in familial schwannomatosis. Schwannomatosis (MIM 162091) is characterized by the 10 Only two families with an INI1 germline mutation, an development of multiple spinal, peripheral, and cranial- exon 4 frameshift mutation,11 and an exon 7 donor splice nerve schwannomas in the absence of vestibular schwan- site mutation12 have been described in which multiple nomas.1 The presence of vestibular schwannomas is di- generations were affected by malignant (rhabdoid) tumors agnostic of neurofibromatosis type 2 (NF2 [MIM 101000]). in infancy. In both of these families, clear cases of no- Molecular analyses identified somatically acquired mu- nexpressing obligate carriers of the INI1 mutation were -
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. -
The H3.3 Chaperone Hira Complex Orchestrates Oocyte Developmental Competence
bioRxiv preprint doi: https://doi.org/10.1101/2020.05.25.114124; this version posted May 26, 2020. 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. The H3.3 chaperone Hira complex orchestrates oocyte developmental competence Rowena Smith1, *, Zongliang Jiang2, *, Andrej Susor3, Hao Ming2, Janet Tait1, Marco Conti4, and Chih-Jen Lin1,5 1MRC Centre For Reproductive Health, University oF Edinburgh Queen’s Medical Research Institute 47 Little France Crescent, Edinburgh, United Kingdom, EH16 4TJ 2 School oF Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, 70803, USA 3 Laboratory oF Biochemistry and Molecular Biology oF Germ Cells, Institute oF Animal Physiology and Genetics, CAS, Rumburska 89, 277 21 Libechov, Czech Republic 4Center For Reproductive Sciences, University oF CaliFornia, San Francisco, CA 94143, USA 5To whom correspondence should be addressed. Tel: +44 131 242 6237; Email: [email protected] *equal contribution bioRxiv preprint doi: https://doi.org/10.1101/2020.05.25.114124; this version posted May 26, 2020. 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 Reproductive success relies on a healthy oocyte competent For Fertilisation and capable of sustaining early embryo development. By the end oF oogenesis, the oocyte is characterised by a transcriptionally silenced state, but the signiFicance oF this state and how it is achieved remains poorly understood. -
Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’S Biological Network Based on Systematic Pharmacology
ORIGINAL RESEARCH published: 25 June 2021 doi: 10.3389/fphar.2021.601846 Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology Kailin Yang 1†, Liuting Zeng 1†, Anqi Ge 2†, Yi Chen 1†, Shanshan Wang 1†, Xiaofei Zhu 1,3† and Jinwen Ge 1,4* Edited by: 1 Takashi Sato, Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of 2 Tokyo University of Pharmacy and Life Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China, Galactophore Department, The First 3 Sciences, Japan Hospital of Hunan University of Chinese Medicine, Changsha, China, School of Graduate, Central South University, Changsha, China, 4Shaoyang University, Shaoyang, China Reviewed by: Hui Zhao, Capital Medical University, China Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Maria Luisa Del Moral, fi University of Jaén, Spain Rhizoma Compound (HCC) has de nite curative effect on cerebral ischemic diseases, *Correspondence: such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its Jinwen Ge mechanism for treating cerebral ischemia is still not fully explained. [email protected] †These authors share first authorship Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. Specialty section: The CIR genes were obtained from Genecards and OMIM and the protein-protein This article was submitted to interaction (PPI) data of HCC’s targets and IS genes were obtained from String Ethnopharmacology, a section of the journal database. -
APBA2 Antibody A
C 0 2 - t APBA2 Antibody a e r o t S Orders: 877-616-CELL (2355) [email protected] Support: 877-678-TECH (8324) 3 9 Web: [email protected] 5 www.cellsignal.com 8 # 3 Trask Lane Danvers Massachusetts 01923 USA For Research Use Only. Not For Use In Diagnostic Procedures. Applications: Reactivity: Sensitivity: MW (kDa): Source: UniProt ID: Entrez-Gene Id: WB, IP M R Endogenous 135 Rabbit Q99767 321 Product Usage Information Application Dilution Western Blotting 1:1000 Immunoprecipitation 1:50 Storage Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody. Specificity / Sensitivity APBA2 Antibody recognizes endogenous levels of total APBA2 protein. Species Reactivity: Mouse, Rat Species predicted to react based on 100% sequence homology: Human Source / Purification Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Phe300 of human APBA2 protein. Antibodies are purified by protein A and peptide affinity chromatography. Background Amyloid β A4 precursor protein-binding family A member 2 (APBA2) is a neuronal adaptor protein that interacts with the amyloid β precursor protein (APP) (1). The amyloid β-protein (Aβ) is the principal component of amyloid plaques, a pathological hallmark of Alzheimer’s disease (2). APBA2 has been shown to stabilize APP metabolism and suppress the secretion of Aβ (3). APBA2 mediates interaction between APP and the neural type I membrane protein Alcadein (Alc) by linking their cytoplasmic domains, thereby forming a tripartite complex of the three proteins in neurons (4). -
Mechanisms of Synaptic Plasticity Mediated by Clathrin Adaptor-Protein Complexes 1 and 2 in Mice
Mechanisms of synaptic plasticity mediated by Clathrin Adaptor-protein complexes 1 and 2 in mice Dissertation for the award of the degree “Doctor rerum naturalium” at the Georg-August-University Göttingen within the doctoral program “Molecular Biology of Cells” of the Georg-August University School of Science (GAUSS) Submitted by Ratnakar Mishra Born in Birpur, Bihar, India Göttingen, Germany 2019 1 Members of the Thesis Committee Prof. Dr. Peter Schu Institute for Cellular Biochemistry, (Supervisor and first referee) University Medical Center Göttingen, Germany Dr. Hans Dieter Schmitt Neurobiology, Max Planck Institute (Second referee) for Biophysical Chemistry, Göttingen, Germany Prof. Dr. med. Thomas A. Bayer Division of Molecular Psychiatry, University Medical Center, Göttingen, Germany Additional Members of the Examination Board Prof. Dr. Silvio O. Rizzoli Department of Neuro-and Sensory Physiology, University Medical Center Göttingen, Germany Dr. Roland Dosch Institute of Developmental Biochemistry, University Medical Center Göttingen, Germany Prof. Dr. med. Martin Oppermann Institute of Cellular and Molecular Immunology, University Medical Center, Göttingen, Germany Date of oral examination: 14th may 2019 2 Table of Contents List of abbreviations ................................................................................. 5 Abstract ................................................................................................... 7 Chapter 1: Introduction ............................................................................ -
Control Association Analysis of CABIN1 with Schizophrenia in a Japanese Population
Journal of Human Genetics (2010) 55, 179–181 & 2010 The Japan Society of Human Genetics All rights reserved 1434-5161/10 $32.00 www.nature.com/jhg SHORT COMMUNICATION A case–control association analysis of CABIN1 with schizophrenia in a Japanese population Yuichiro Watanabe1,2, Ayako Nunokawa1, Naoshi Kaneko1 and Toshiyuki Someya1 Calcineurin (CN) is a calcium/calmodulin-dependent serine/threonine protein phosphatase and regulates neuronal structure, neurotransmission and activity-dependent gene expression. Several studies have indicated that CN signaling is likely to be involved in the pathogenesis of schizophrenia. The gene encoding CN-binding protein 1 (CABIN1) is located on 22q11.23, one of the common susceptibility loci for schizophrenia. Therefore, CABIN1 is a promising functional and positional candidate gene for schizophrenia. To assess whether CABIN1 is implicated in vulnerability to schizophrenia, we conducted a case–control association study between CABIN1 and schizophrenia. The results showed no evidence of an association between CABIN1 and schizophrenia using 11 tagging single nucleotide polymorphisms in 1193 Japanese subjects. Our results suggest that CABIN1 may not confer increased susceptibility for schizophrenia in the Japanese population. Journal of Human Genetics (2010) 55, 179–181; doi:10.1038/jhg.2009.136; published online 15 January 2010 Keywords: CABIN1; case–control study; schizophrenia; tagging SNP Schizophrenia is a complex genetic disorder that affects approximately one study. Fallin et al.10 examined seven polymorphisms in CABIN1 1% of the global population. The pathogenesis of schizophrenia is with an average density of one marker per 20.9 kb and failed to find currently unclear, but there is cumulative evidence that calcineurin any association with schizophrenia.