Learning-Induced and Stathmin-Dependent Changes in Microtubule Stability Are Critical for Memory and Disrupted in Ageing
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Universidade Estadual De Campinas Instituto De Biologia
UNIVERSIDADE ESTADUAL DE CAMPINAS INSTITUTO DE BIOLOGIA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA CAMPINAS 2016 1 VERÔNICA APARECIDA MONTEIRO SAIA CEREDA O PROTEOMA DO CORPO CALOSO DA ESQUIZOFRENIA THE PROTEOME OF THE CORPUS CALLOSUM IN SCHIZOPHRENIA Dissertação apresentada ao Instituto de Biologia da Universidade Estadual de Campinas como parte dos requisitos exigidos para a obtenção do Título de Mestra em Biologia Funcional e Molecular na área de concentração de Bioquímica. Dissertation presented to the Institute of Biology of the University of Campinas in partial fulfillment of the requirements for the degree of Master in Functional and Molecular Biology, in the area of Biochemistry. ESTE ARQUIVO DIGITAL CORRESPONDE À VERSÃO FINAL DA DISSERTAÇÃO DEFENDIDA PELA ALUNA VERÔNICA APARECIDA MONTEIRO SAIA CEREDA E ORIENTADA PELO DANIEL MARTINS-DE-SOUZA. Orientador: Daniel Martins-de-Souza CAMPINAS 2016 2 Agência(s) de fomento e nº(s) de processo(s): CNPq, 151787/2F2014-0 Ficha catalográfica Universidade Estadual de Campinas Biblioteca do Instituto de Biologia Mara Janaina de Oliveira - CRB 8/6972 Saia-Cereda, Verônica Aparecida Monteiro, 1988- Sa21p O proteoma do corpo caloso da esquizofrenia / Verônica Aparecida Monteiro Saia Cereda. – Campinas, SP : [s.n.], 2016. Orientador: Daniel Martins de Souza. Dissertação (mestrado) – Universidade Estadual de Campinas, Instituto de Biologia. 1. Esquizofrenia. 2. Espectrometria de massas. 3. Corpo caloso. -
UCSD MOLECULE PAGES Doi:10.6072/H0.MP.A002549.01 Volume 1, Issue 2, 2012 Copyright UC Press, All Rights Reserved
UCSD MOLECULE PAGES doi:10.6072/H0.MP.A002549.01 Volume 1, Issue 2, 2012 Copyright UC Press, All rights reserved. Review Article Open Access WAVE2 Tadaomi Takenawa1, Shiro Suetsugu2, Daisuke Yamazaki3, Shusaku Kurisu1 WASP family verprolin-homologous protein 2 (WAVE2, also called WASF2) was originally identified by its sequence similarity at the carboxy-terminal VCA (verprolin, cofilin/central, acidic) domain with Wiskott-Aldrich syndrome protein (WASP) and N-WASP (neural WASP). In mammals, WAVE2 is ubiquitously expressed, and its two paralogs, WAVE1 (also called suppressor of cAMP receptor 1, SCAR1) and WAVE3, are predominantly expressed in the brain. The VCA domain of WASP and WAVE family proteins can activate the actin-related protein 2/3 (Arp2/3) complex, a major actin nucleator in cells. Proteins that can activate the Arp2/3 complex are now collectively known as nucleation-promoting factors (NPFs), and the WASP and WAVE families are a founding class of NPFs. The WAVE family has an amino-terminal WAVE homology domain (WHD domain, also called the SCAR homology domain, SHD) followed by the proline-rich region that interacts with various Src-homology 3 (SH3) domain proteins. The VCA domain located at the C-terminus. WAVE2, like WAVE1 and WAVE3, constitutively forms a huge heteropentameric protein complex (the WANP complex), binding through its WHD domain with Abi-1 (or its paralogs, Abi-2 and Abi-3), HSPC300 (also called Brick1), Nap1 (also called Hem-2 and NCKAP1), Sra1 (also called p140Sra1 and CYFIP1; its paralog is PIR121 or CYFIP2). The WANP complex is recruited to the plasma membrane by cooperative action of activated Rac GTPases and acidic phosphoinositides. -
Conserved Microtubule–Actin Interactions in Cell Movement and Morphogenesis
REVIEW Conserved microtubule–actin interactions in cell movement and morphogenesis Olga C. Rodriguez, Andrew W. Schaefer, Craig A. Mandato, Paul Forscher, William M. Bement and Clare M. Waterman-Storer Interactions between microtubules and actin are a basic phenomenon that underlies many fundamental processes in which dynamic cellular asymmetries need to be established and maintained. These are processes as diverse as cell motility, neuronal pathfinding, cellular wound healing, cell division and cortical flow. Microtubules and actin exhibit two mechanistic classes of interactions — regulatory and structural. These interactions comprise at least three conserved ‘mechanochemical activity modules’ that perform similar roles in these diverse cell functions. Over the past 35 years, great progress has been made towards under- crosstalk occurs in processes that require dynamic cellular asymme- standing the roles of the microtubule and actin cytoskeletal filament tries to be established or maintained to allow rapid intracellular reor- systems in mechanical cellular processes such as dynamic shape ganization or changes in shape or direction in response to stimuli. change, shape maintenance and intracellular organelle movement. Furthermore, the widespread occurrence of these interactions under- These functions are attributed to the ability of polarized cytoskeletal scores their importance for life, as they occur in diverse cell types polymers to assemble and disassemble rapidly, and to interact with including epithelia, neurons, fibroblasts, oocytes and early embryos, binding proteins and molecular motors that mediate their regulated and across species from yeast to humans. Thus, defining the mecha- movement and/or assembly into higher order structures, such as radial nisms by which actin and microtubules interact is key to understand- arrays or bundles. -
Absence of NEFL in Patient-Specific Neurons in Early-Onset Charcot-Marie-Tooth Neuropathy Markus T
ARTICLE OPEN ACCESS Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy Markus T. Sainio, MSc, Emil Ylikallio, MD, PhD, Laura M¨aenp¨a¨a, MSc, Jenni Lahtela, PhD, Pirkko Mattila, PhD, Correspondence Mari Auranen, MD, PhD, Johanna Palmio, MD, PhD, and Henna Tyynismaa, PhD Dr. Tyynismaa [email protected] Neurol Genet 2018;4:e244. doi:10.1212/NXG.0000000000000244 Abstract Objective We used patient-specific neuronal cultures to characterize the molecular genetic mechanism of recessive nonsense mutations in neurofilament light (NEFL) underlying early-onset Charcot- Marie-Tooth (CMT) disease. Methods Motor neurons were differentiated from induced pluripotent stem cells of a patient with early- onset CMT carrying a novel homozygous nonsense mutation in NEFL. Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons. Results We show that the recessive nonsense mutation causes a nearly total loss of NEFL messenger RNA (mRNA), leading to the complete absence of NEFL protein in patient’s cultured neurons. Yet the cultured neurons were able to differentiate and form neuronal networks and neuro- filaments. Single-neuron gene expression fingerprinting pinpointed NEFL as the most down- regulated gene in the patient neurons and provided data of intermediate filament transcript abundancy and dynamics in cultured neurons. Blocking of nonsense-mediated decay partially rescued the loss of NEFL mRNA. Conclusions The strict neuronal specificity of neurofilament has hindered the mechanistic studies of re- cessive NEFL nonsense mutations. Here, we show that such mutation leads to the absence of NEFL, causing childhood-onset neuropathy through a loss-of-function mechanism. -
Stathmin Is Overexpressed in Malignant Mesothelioma
ANTICANCER RESEARCH 27: 39-44 (2007) Stathmin is Overexpressed in Malignant Mesothelioma JAE Y. KIM1, CHANSONETTE HARVARD1, LIANG YOU1, ZHIDONG XU1, KRISTOPHER KUCHENBECKER1, RICK BAEHNER2 and DAVID JABLONS1 1Thoracic Oncology Laboratory, UCSF Comprehensive Cancer Center, San Francisco, CA 94115; 2Department of Pathology, UCSF, San Francisco, CA 94115, U.S.A. Abstract. Background: Malignant pleural mesothelioma is a unclear (7, 8). Unlike many other epithelial cancers, the highly aggressive cancer, with low overall survival. The activation of ras genes and inactivation of Rb and p53 genes pathogenesis of mesothelioma is poorly understood. The aim of do not seem to be necessary for the development of this study was to identify potential genes overexpressed in mesothelioma (9, 10). Alterations of several molecular mesothelioma. Materials and Methods: A cDNA microarray was pathways, including epidermal growth factor receptor, cell used to identify potential genes that are activated in mesothelioma cycle regulatory genes, and developmental pathways have cell lines. Overexpression of stathmin, a cytosolic protein that been linked to mesothelioma (11, 12). There is also regulates microtubule dynamics, was found. RT-PCR, Western evidence that Simian virus 40 (SV40) may contribute to the blot, and immunohistochemistry were used to confirm develop of mesothelioma, but the exact genetic alterations overexpression in both cell lines and tumor samples. Results: leading to mesothelioma remain unknown (11, 13). Using RT-PCR and Western blot, stathmin overexpression was The aim of this study was to identify potential genes confirmed in seven mesothelioma cell lines. Increased stathmin involved in the pathogenesis of mesothelioma. protein expression was also found in seven out of eight mesothelioma tumor samples. -
Microtubule-Associated Protein Tau (Molecular Pathology/Neurodegenerative Disease/Neurofibriliary Tangles) M
Proc. Nati. Acad. Sci. USA Vol. 85, pp. 4051-4055, June 1988 Medical Sciences Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau (molecular pathology/neurodegenerative disease/neurofibriliary tangles) M. GOEDERT*, C. M. WISCHIK*t, R. A. CROWTHER*, J. E. WALKER*, AND A. KLUG* *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; and tDepartment of Psychiatry, University of Cambridge Clinical School, Hills Road, Cambridge CB2 2QQ, United Kingdom Contributed by A. Klug, March 1, 1988 ABSTRACT Screening of cDNA libraries prepared from (21). This task is made all the more difficult because there is the frontal cortex ofan zheimer disease patient and from fetal no functional or physiological assay for the protein(s) of the human brain has led to isolation of the cDNA for a core protein PHF. The only identification so far possible is the morphol- of the paired helical fiament of Alzheimer disease. The partial ogy of the PHFs at the electron microscope level, and here amino acid sequence of this core protein was used to design we would accept only experiments on isolated individual synthetic oligonucleotide probes. The cDNA encodes a protein of filaments, not on neurofibrillary tangles (in which other 352 amino acids that contains a characteristic amino acid repeat material might be occluded). One thus needs a label or marker in its carboxyl-terminal half. This protein is highly homologous for the PHF itself, which can at the same time be used to to the sequence ofthe mouse microtubule-assoiated protein tau follow the steps of the biochemical purification. -
Neurofilaments: Neurobiological Foundations for Biomarker Applications
Neurofilaments: neurobiological foundations for biomarker applications Arie R. Gafson1, Nicolas R. Barthelmy2*, Pascale Bomont3*, Roxana O. Carare4*, Heather D. Durham5*, Jean-Pierre Julien6,7*, Jens Kuhle8*, David Leppert8*, Ralph A. Nixon9,10,11,12*, Roy Weller4*, Henrik Zetterberg13,14,15,16*, Paul M. Matthews1,17 1 Department of Brain Sciences, Imperial College, London, UK 2 Department of Neurology, Washington University School of Medicine, St Louis, MO, USA 3 a ATIP-Avenir team, INM, INSERM , Montpellier university , Montpellier , France. 4 Clinical Neurosciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom 5 Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada 6 Department of Psychiatry and Neuroscience, Laval University, Quebec, Canada. 7 CERVO Brain Research Center, 2601 Chemin de la Canardière, Québec, QC, G1J 2G3, Canada 8 Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland. 9 Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY, 10962, USA. 10Departments of Psychiatry, New York University School of Medicine, New York, NY, 10016, 11 Neuroscience Institute, New York University School of Medicine, New York, NY, 10016, USA. 12Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA 13 University College London Queen Square Institute of Neurology, London, UK 14 UK Dementia Research Institute at University College London 15 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden 16 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden 17 UK Dementia Research Institute at Imperial College, London * Co-authors ordered alphabetically Address for correspondence: Prof. -
Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes
Tohoku J. Exp. Med., 2011,Differential 223, 161-176 Gene Expression in OPCs, Oligodendrocytes and Type II Astrocytes 161 Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes Jian-Guo Hu,1,2,* Yan-Xia Wang,3,* Jian-Sheng Zhou,2 Chang-Jie Chen,4 Feng-Chao Wang,1 Xing-Wu Li1 and He-Zuo Lü1,2 1Department of Clinical Laboratory Science, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China 2Anhui Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu, P.R. China 3Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China 4Department of Laboratory Medicine, Bengbu Medical College, Bengbu, P.R. China Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. -
The Role of the Rho Gtpases in Neuronal Development
Downloaded from genesdev.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The role of the Rho GTPases in neuronal development Eve-Ellen Govek,1,2, Sarah E. Newey,1 and Linda Van Aelst1,2,3 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA; 2Molecular and Cellular Biology Program, State University of New York at Stony Brook, Stony Brook, New York, 11794, USA Our brain serves as a center for cognitive function and and an inactive GDP-bound state. Their activity is de- neurons within the brain relay and store information termined by the ratio of GTP to GDP in the cell and can about our surroundings and experiences. Modulation of be influenced by a number of different regulatory mol- this complex neuronal circuitry allows us to process that ecules. Guanine nucleotide exchange factors (GEFs) ac- information and respond appropriately. Proper develop- tivate GTPases by enhancing the exchange of bound ment of neurons is therefore vital to the mental health of GDP for GTP (Schmidt and Hall 2002); GTPase activat- an individual, and perturbations in their signaling or ing proteins (GAPs) act as negative regulators of GTPases morphology are likely to result in cognitive impairment. by enhancing the intrinsic rate of GTP hydrolysis of a The development of a neuron requires a series of steps GTPase (Bernards 2003; Bernards and Settleman 2004); that begins with migration from its birth place and ini- and guanine nucleotide dissociation inhibitors (GDIs) tiation of process outgrowth, and ultimately leads to dif- prevent exchange of GDP for GTP and also inhibit the ferentiation and the formation of connections that allow intrinsic GTPase activity of GTP-bound GTPases (Zalc- it to communicate with appropriate targets. -
Early Growth Response 1 Regulates Hematopoietic Support and Proliferation in Human Primary Bone Marrow Stromal Cells
Hematopoiesis SUPPLEMENTARY APPENDIX Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells Hongzhe Li, 1,2 Hooi-Ching Lim, 1,2 Dimitra Zacharaki, 1,2 Xiaojie Xian, 2,3 Keane J.G. Kenswil, 4 Sandro Bräunig, 1,2 Marc H.G.P. Raaijmakers, 4 Niels-Bjarne Woods, 2,3 Jenny Hansson, 1,2 and Stefan Scheding 1,2,5 1Division of Molecular Hematology, Department of Laboratory Medicine, Lund University, Lund, Sweden; 2Lund Stem Cell Center, Depart - ment of Laboratory Medicine, Lund University, Lund, Sweden; 3Division of Molecular Medicine and Gene Therapy, Department of Labora - tory Medicine, Lund University, Lund, Sweden; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands and 5Department of Hematology, Skåne University Hospital Lund, Skåne, Sweden ©2020 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2019.216648 Received: January 14, 2019. Accepted: July 19, 2019. Pre-published: August 1, 2019. Correspondence: STEFAN SCHEDING - [email protected] Li et al.: Supplemental data 1. Supplemental Materials and Methods BM-MNC isolation Bone marrow mononuclear cells (BM-MNC) from BM aspiration samples were isolated by density gradient centrifugation (LSM 1077 Lymphocyte, PAA, Pasching, Austria) either with or without prior incubation with RosetteSep Human Mesenchymal Stem Cell Enrichment Cocktail (STEMCELL Technologies, Vancouver, Canada) for lineage depletion (CD3, CD14, CD19, CD38, CD66b, glycophorin A). BM-MNCs from fetal long bones and adult hip bones were isolated as reported previously 1 by gently crushing bones (femora, tibiae, fibulae, humeri, radii and ulna) in PBS+0.5% FCS subsequent passing of the cell suspension through a 40-µm filter. -
The Relationship Between Intermediate Filaments and Microfilaments Before and During the Formation of Desmosomes and Adherens-Ty
Published May 1, 1987 The Relationship between Intermediate Filaments and Microfilaments before and during the Formation of Desmosomes and Adherens-type Junctions in Mouse Epidermal Keratinocytes Kathleen J. Green, Benjamin Geiger,* Jonathan C. R. Jones, John C. Talian, and Robert D. Goldman Department of Cell Biology and Anatomy, Northwestern University Medical School, Chicago, Illinois 60611; and * Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel Abstract. Actin, keratin, vinculin and desmoplakin ermost of the concentric MFB. Individual IF often organization were studied in primary mouse keratino- splay out, becoming interwoven into these MFB in the cytes before and during Ca2+-induced cell contact forma- region of cell-substrate contact. In the first 30 min af- tion. Double-label fluorescence shows that in cells cul- ter the Ca 2+ switch, areas of submembranous dense Downloaded from tured in low Ca 2÷ medium, keratin-containing inter- material (identified as adherens junctions), which are mediate filament bundles (IFB) and desmoplakin- associated with the perpendicular MFB, can be seen at containing spots are both concentrated towards the cell newly formed cell-ceU contact sites. By 1-2 h, IFB- center in a region bounded by a series of concentric desmosomal component complexes are aligned with microfilament bundles (MFB). Within 5-30 min after the perpendicular MFB as the complexes become jcb.rupress.org raising Ca 2+ levels, a discontinuous actin/vinculin-rich, redistributed to cell-cell interfaces. Cytochalasin D submembranous zone of fluorescence appears at cell- treatment causes the redistribution of actin into numer- cell interfaces. This zone is usually associated with ous patches; keratin-containing Lr:B undergo a con- short, perpendicular MFB, which become wider and comitant redistribution, forming foci that coincide with longer with time. -
Gene Expression Signatures and Biomarkers of Noninvasive And
Oncogene (2006) 25, 2328–2338 & 2006 Nature Publishing Group All rights reserved 0950-9232/06 $30.00 www.nature.com/onc ORIGINAL ARTICLE Gene expression signatures and biomarkers of noninvasive and invasive breast cancer cells: comprehensive profiles by representational difference analysis, microarrays and proteomics GM Nagaraja1, M Othman2, BP Fox1, R Alsaber1, CM Pellegrino3, Y Zeng2, R Khanna2, P Tamburini3, A Swaroop2 and RP Kandpal1 1Department of Biological Sciences, Fordham University, Bronx, NY, USA; 2Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA and 3Bayer Corporation, West Haven, CT, USA We have characterized comprehensive transcript and Keywords: representational difference analysis; micro- proteomic profiles of cell lines corresponding to normal arrays; proteomics; breast carcinoma; biomarkers; breast (MCF10A), noninvasive breast cancer (MCF7) and copper homeostasis invasive breast cancer (MDA-MB-231). The transcript profiles were first analysed by a modified protocol for representational difference analysis (RDA) of cDNAs between MCF7 and MDA-MB-231 cells. The majority of genes identified by RDA showed nearly complete con- Introduction cordance withmicroarray results, and also led to the identification of some differentially expressed genes such The transformation of a normal cell into a cancer cell as lysyl oxidase, copper transporter ATP7A, EphB6, has been correlated to altered expression of a variety of RUNX2 and a variant of RUNX2. The altered transcripts genes (Perou et al., 2000; Becker et al., 2005). The identified by microarray analysis were involved in cell–cell expression of some of these genes is a direct result of or cell–matrix interaction, Rho signaling, calcium home- sequence mutation, whereas other changes occur due to ostasis and copper-binding/sensitive activities.