Genome-Wide Analyses Identify KIF5A As a Novel ALS Gene
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Supplemental Material Table of Contents
Supplemental material Table of Contents Detailed Materials and Methods ......................................................................................................... 2 Perioperative period ........................................................................................................................... 2 Ethical aspects ................................................................................................................................... 4 Evaluation of heart failure ................................................................................................................. 4 Sample preparation for ANP mRNA expression .................................................................................. 5 Sample preparation for validative qRT-PCR (Postn, Myh7, Gpx3, Tgm2) ............................................ 6 Tissue fibrosis .................................................................................................................................... 7 Ventricular remodeling and histological tissue preservation ................................................................ 8 Evaluation of the histological preservation of cardiac tissue ................................................................ 9 Sample preparation and quantitative label-free proteomics analyses .................................................. 10 Statistical methods ........................................................................................................................... 12 References ........................................................................................................................................ -
Decreased Expression of Profilin 2 in Oral Squamous Cell Carcinoma and Its Clinicopathological Implications
ONCOLOGY REPORTS 26: 813-823, 2011 Decreased expression of profilin 2 in oral squamous cell carcinoma and its clinicopathological implications C.Y. MA1,2, C.P. ZHANG1,2, L.P. ZHONG1,2, H.Y. PAN1,2, W.T. CHEN1,2, L.Z. WANG3, O.W. ANDREW4, T. JI1 and W. HAN1,2 1Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology; 2Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology; 3Department of Oral Pathology, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China; 4Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore 119074, Singapore Received February 8, 2011; Accepted April 11, 2011 DOI: 10.3892/or.2011.1365 Abstract. Profilins are small proteins essential for many clinical and pathological significance. In conclusion, PFN2 normal cellular dynamics and constitute one of the crucial can be utilized as both a potential suppressor marker and a components of actin-based cellular motility. Several recent prognostic protein for OSCC. The function of PFN2 may be to studies have implicated a role for the profilin (PFN) family in regulate the N-WASP/Arp2/3 signaling pathway. cancer pathogenesis and progression. However, their expression and promising functions are largely unknown in oral squamous Introduction cell carcinoma (OSCC). In this study, we analyzed the correlation between PFN1 and PFN2 expression in vitro and Oral squamous cell carcinoma (OSCC) is a significant public in vivo. The protein expression levels were roughly compared health problem with >300,000 new cases being diagnosed between cell lines (HIOEC, HB96) with the employment of annually worldwide (1). -
Analysis of Shared Common Genetic Risk Between Amyotrophic Lateral Sclerosis and Epilepsy
Neurobiology of Aging xxx (2020) 1.e1e1.e5 Contents lists available at ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging Negative results Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy Dick Schijvena,b,c, Remi Stevelinkd, Mark McCormackd,e, Wouter van Rheenena, Jurjen J. Luykxb, Bobby P.C. Koelemand, Jan H. Veldinka,*, on behalf of the Project MinE ALS GWAS Consortium International League Against Epilepsy Consortium on Complex Epilepsies a Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands b Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands c Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands d Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands e Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin, Ireland article info abstract Article history: Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the Received 23 September 2019 latest and largest genome-wide studies in amyotrophic lateral sclerosis (n ¼ 36,052) and epilepsy (n ¼ Received in revised form 31 January 2020 38,349) to determine genetic overlap between these conditions. First, we showed no significant ge- Accepted 10 April 2020 netic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. -
Exploring Profilin
RESEARCH HIGHLIGHTS NEUROTRANSMISSION Exploring profilin DOI: 10.1038/nrn2182 Surprisingly, they found that Pfn2–/– mice, pointing towards a Pfn2–/– mice displayed normal higher vesicle release probability. development and brain anatomy. Immunoprecipitation and EM studies Learning and memory, long-term also indicated that the number of potentiation (LTP) and long-term docked vesicles is approximately 25% depression (LTD) were not impaired higher in Pfn2–/– mice. in Pfn2–/– mice when compared with How does profilin 2 alter vesicle control mice. These results suggest release? When neurotransmitter that profilin 2 is not required for secretion was stimulated in cortical development, synaptic plasticity or synaptosomes from control mice, learning and memory. F-actin levels were significantly The authors noticed, however, increased. This did not occur in that the Pfn2–/– mice behaved synaptosome preparations from differently to control mice. They Pfn2–/– mice. In addition, profilin 2, were hyperactive, and they showed but not profilin 1, was shown to be elevated exploratory and novelty- tightly associated with the WAVE- Profilins are regulators of actin seeking behaviour when placed into complex, a protein complex that is polymerization. Profilin 2 is a new environment. This included implicated in actin dynamics and expressed mainly in neurons, but increased locomotor activity, wall is abundant in synaptosomal prepa- its specific function is unknown. A rearings and rearings in the centre of rations. The authors therefore study by Boyl et al. provides evidence the experimental area. Conversely, suggest that WAVE and profilin 2 that profilin 2 is required for activ- in the familiar environment of their might cooperate to restrict synaptic ity-stimulated actin polymerization home cage, they showed reduced vesicle release. -
Profilin and Formin Constitute a Pacemaker System for Robust Actin
RESEARCH ARTICLE Profilin and formin constitute a pacemaker system for robust actin filament growth Johanna Funk1, Felipe Merino2, Larisa Venkova3, Lina Heydenreich4, Jan Kierfeld4, Pablo Vargas3, Stefan Raunser2, Matthieu Piel3, Peter Bieling1* 1Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany; 2Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany; 3Institut Curie UMR144 CNRS, Paris, France; 4Physics Department, TU Dortmund University, Dortmund, Germany Abstract The actin cytoskeleton drives many essential biological processes, from cell morphogenesis to motility. Assembly of functional actin networks requires control over the speed at which actin filaments grow. How this can be achieved at the high and variable levels of soluble actin subunits found in cells is unclear. Here we reconstitute assembly of mammalian, non-muscle actin filaments from physiological concentrations of profilin-actin. We discover that under these conditions, filament growth is limited by profilin dissociating from the filament end and the speed of elongation becomes insensitive to the concentration of soluble subunits. Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-actin concentrations. We demonstrate that mammalian cells indeed operate at the limit to actin filament growth imposed by profilin and formins. Our results reveal how synergy between profilin and formins generates robust filament growth rates that are resilient to changes in the soluble subunit concentration. DOI: https://doi.org/10.7554/eLife.50963.001 *For correspondence: peter.bieling@mpi-dortmund. mpg.de Introduction Competing interests: The Eukaryotic cells move, change their shape and organize their interior through dynamic actin net- authors declare that no works. -
Epigenetic Regulation of Smad2 and Smad3 by Profilin-2 Promotes Lung Cancer Growth and Metastasis
ARTICLE Received 26 May 2014 | Accepted 29 Jul 2015 | Published 10 Sep 2015 DOI: 10.1038/ncomms9230 Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis Yun-Neng Tang1, Wei-Qiao Ding1, Xiao-Jie Guo1, Xin-Wang Yuan1, Dong-Mei Wang1 & Jian-Guo Song1 Altered transforming growth factor-b (TGF-b) signalling has been implicated in tumour development and progression. However, the molecular mechanism behind this alteration is poorly understood. Here we show that profilin-2 (Pfn2) increases Smad2 and Smad3 expression via an epigenetic mechanism, and that profilin-2 and Smad expression correlate with an unfavourable prognosis of lung cancer patients. Profilin-2 overexpression promotes, whereas profilin-2 knockdown drastically reduces, lung cancer growth and metastasis. We show that profilin-2 suppresses the recruitment of HDAC1 to Smad2 and Smad3 promoters by preventing nuclear translocation of HDAC1 through protein–protein interaction at the C terminus of both proteins, leading to the transcriptional activation of Smad2 and Smad3. Increased Smad2 and Smad3 expression enhances TGF-b1-induced EMT and production of the angiogenic factors VEGF and CTGF. These findings reveal a new regulatory mechanism of TGF-b1/Smad signalling, and suggest a potential molecular target for the development of anticancer drugs. 1 State Key Laboratory of Cell Biology, Innovation Center for Cell Signalling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Correspondence and requests for materials should be addressed to J.-G.S. (email: [email protected]). NATURE COMMUNICATIONS | 6:8230 | DOI: 10.1038/ncomms9230 | www.nature.com/naturecommunications 1 & 2015 Macmillan Publishers Limited. -
Evaluation of Profilin 1 As a Biomarker in Myocardial Infarction
European Review for Medical and Pharmacological Sciences 2020; 24: 8112-8116 Evaluation of profilin 1 as a biomarker in myocardial infarction 1 2 3 2 1 1 E. PASZEK , K ŻMUDKA , K. PLENS , J. LEGUTKO , T. RAJS , W. ZAJDEL 1Department of Interventional Cardiology, Institute of Cardiology, John Paul II Hospital, Kraków, Poland 2Jagiellonian University Medical College, Institute of Cardiology, Department of Interventional Cardiology, John Paul II Hospital, Kraków, Poland 3KCRI, Kraków, Poland Abstract. – OBJECTIVE: Profilin 1 Pfn1)( is Introduction likely to be involved in atherogenesis and myo- cardial infarction (MI). Clinical data on this sub- Profilin 1 (Pfn1) is a small, ubiquitous protein ject are very limited. The aim of this study was involved in actin cytoskeleton regulation. Recent to search for associations between serum Pfn1 studies1,2 show a probable link between Pfn1 and and a number of parameters in MI patients: symp- tom onset to PCI time (OPT), myocardial necrosis the pathogenesis of atherosclerosis and myocar- markers, thrombolysis in myocardial infarction dial infarction. So far, data on this subject are (TIMI) flow, antiplatelet drugs, heparin adminis- very limited and mostly come from in vitro and tration and typical atherosclerosis risk factors. animal models. The time of ischemia duration in PATIENTS AND METHODS: We included pa- myocardial infarction (MI) is a crucial parameter tients with type 1 MI (according to the Third Uni- for clinical decision-making and patient progno- versal Definition of Myocardial Infarction) who sis3. In a clinical setting a parameter derived from were able to precisely determine the time of symp- ischemia time – the time from symptom onset to tom onset. -
Value of Systematic Genetic Screening of Patients with Amyotrophic Lateral
Neurodegeneration J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-325014 on 14 February 2021. Downloaded from Original research Value of systematic genetic screening of patients with amyotrophic lateral sclerosis Stephanie R Shepheard ,1 Matthew D Parker,1 Johnathan Cooper- Knock ,1 Nick S Verber,1 Lee Tuddenham,1 Paul Heath,1 Nick Beauchamp,2 Elsie Place,2 Elizabeth S A Sollars,2 Martin R Turner ,3 Andrea Malaspina,4 Pietro Fratta,5,6 Channa Hewamadduma,7 Thomas M Jenkins ,1 Christopher J McDermott ,1 Dennis Wang,8 Janine Kirby,1 Pamela J Shaw ,1,7 on behalf of the Project MINE Consortium ► Additional material is ABSTRACT mild cognitive impairment, with approximately published online only. To view, Objective The clinical utility of routine genetic 5% progressing to clinically recognised fronto- please visit the journal online 1 (http:// dx. doi. org/ 10. 1136/ sequencing in amyotrophic lateral sclerosis (ALS) is temporal dementia (FTD). While the majority of jnnp- 2020- 325014). uncertain. Our aim was to determine whether routine ALS cases are considered sporadic (sALS), 5%–10% targeted sequencing of 44 ALS- relevant genes would have been shown to be familial, usually with auto- For numbered affiliations see have a significant impact on disease subclassification somal dominant inheritance, and the genetic cause end of article. and clinical care. of approximately 60%–70% of familial ALS (fALS) 2 Methods We performed targeted sequencing of a 44- cases has now been identified. The most common Correspondence to Professor Pamela J Shaw, gene panel in a prospective case series of 100 patients genetic cause of ALS is due to expansion of a Sheffield Institute for with ALS recruited consecutively from the Sheffield GGGGCC (G4C2) hexanucleotide repeat in the Translational Neuroscience, The Motor Neuron Disorders Clinic, UK. -
Cofilin-1 Phosphorylation Catalyzed by ERK1/2 Alters Cardiac Actin
Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation Maria Chatzifrangkeskou, David Yadin, Thibaut Marais, Solenne Chardonnet, Mathilde Cohen-Tannoudji, Nathalie Mougenot, Alain Schmitt, Silvia Crasto, Elisa Di Pasquale, Coline Macquart, et al. To cite this version: Maria Chatzifrangkeskou, David Yadin, Thibaut Marais, Solenne Chardonnet, Mathilde Cohen- Tannoudji, et al.. Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation. Human Molecular Genetics, Oxford University Press (OUP), 2018, 27 (17), pp.3060-3078. 10.1093/hmg/ddy215. hal-01962065 HAL Id: hal-01962065 https://hal.sorbonne-universite.fr/hal-01962065 Submitted on 14 Jan 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation Maria Chatzifrangkeskou1, David Yadin2, Thibaut Marais1, Solenne Chardonnet3, Mathilde Cohen-Tannoudji1, Nathalie Mougenot4, Alain Schmitt5, Silvia Crasto6,7, Elisa Di Pasquale6,7, Coline Macquart1, Yannick Tanguy1, Imen Jebeniani8, Michel Puce´at8, Blanca Morales Rodriguez1, Wolfgang H. Goldmann9, Matteo Dal Ferro10, Maria-Grazia Biferi1, Petra Knaus2, Gise`le Bonne1, Howard J. -
Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients Authors
Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients Authors: Wen-Ling Liao1,2, Chiz-Tzung Chang3,4, Ching-Chu Chen5,6, Wen-Jane Lee7,8, Shih-Yi Lin3,4, Hsin-Yi Liao9, Chia-Ming Wu10, Ya-Wen Chang10, Chao-Jung Chen1,9,+,*, Fuu-Jen Tsai6,10,11,+,* 1 Graduate Institute of Integrated Medicine, China Medical University, Taichung, 404, Taiwan 2 Center for Personalized Medicine, China Medical University Hospital, Taichung, 404, Taiwan 3 Division of Nephrology and Kidney Institute, Department of Internal Medicine, China Medical University Hospital, Taichung, 404, Taiwan 4 Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, 404, Taiwan 5 Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, 404, Taiwan 6 School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan 7 Department of Medical Research, Taichung Veterans General Hospital, Taichung, 404, Taiwan 8 Department of Social Work, Tunghai University, Taichung, 404, Taiwan 9 Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan 10 Human Genetic Center, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan 11 Department of Health and Nutrition Biotechnology, Asia University, Taichung, 404, Taiwan + Fuu-Jen Tsai and Chao-Jung Chen contributed equally to this work. Correspondence: Fuu-Jen Tsai, MD, PhD and Chao-Jung Chen, PhD FJ Tsai: Genetic Center, China Medical University Hospital, No.2 Yuh-Der Road, 404 Taichung, Taiwan; Telephone: 886-4-22062121 Ext. 2041; Fax: 886-4-22033295; E-mail: [email protected] CJ Chen: Graduate Institute of Integrated Medicine, China Medical University, No.91, Hsueh-Shih Road, 404, Taichung, Taiwan; Telephone: 886-4-22053366 Ext. -
Disrupted Neuronal Trafficking in Amyotrophic Lateral Sclerosis
Acta Neuropathologica (2019) 137:859–877 https://doi.org/10.1007/s00401-019-01964-7 REVIEW Disrupted neuronal trafcking in amyotrophic lateral sclerosis Katja Burk1,2 · R. Jeroen Pasterkamp3 Received: 12 October 2018 / Revised: 19 January 2019 / Accepted: 19 January 2019 / Published online: 5 February 2019 © The Author(s) 2019 Abstract Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disease caused by degeneration of motor neurons in the brain and spinal cord leading to muscle weakness. Median survival after symptom onset in patients is 3–5 years and no efective therapies are available to treat or cure ALS. Therefore, further insight is needed into the molecular and cellular mechanisms that cause motor neuron degeneration and ALS. Diferent ALS disease mechanisms have been identi- fed and recent evidence supports a prominent role for defects in intracellular transport. Several diferent ALS-causing gene mutations (e.g., in FUS, TDP-43, or C9ORF72) have been linked to defects in neuronal trafcking and a picture is emerging on how these defects may trigger disease. This review summarizes and discusses these recent fndings. An overview of how endosomal and receptor trafcking are afected in ALS is followed by a description on dysregulated autophagy and ER/ Golgi trafcking. Finally, changes in axonal transport and nucleocytoplasmic transport are discussed. Further insight into intracellular trafcking defects in ALS will deepen our understanding of ALS pathogenesis and will provide novel avenues for therapeutic intervention. Keywords Amyotrophic lateral sclerosis · Motor neuron · Trafcking · Cytoskeleton · Rab Introduction onset is about 10 years earlier [44]. As disease progresses, corticospinal motor neurons, projecting from the motor cor- Amyotrophic lateral sclerosis (ALS) is a fatal disease char- tex to the brainstem and spinal cord, and bulbar and spinal acterized by the degeneration of upper and lower motor motor neurons, projecting to skeletal muscles, degenerate. -
The Universal Mechanism of Intermediate Filament Transport
bioRxiv preprint doi: https://doi.org/10.1101/251405; this version posted January 22, 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. 1 The universal mechanism of intermediate filament transport. 2 3 Amélie Robert1, Peirun Tian1, Stephen A. Adam1, Robert D. Goldman1 and Vladimir I. Gelfand1* 4 5 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern 6 University, Chicago, IL 60611, USA. 7 8 *Corresponding author. 9 Address: Department of Cell and Molecular Biology, Feinberg School of Medicine, 10 Northwestern University, 303 E. Chicago Ave. Ward 11-100, Chicago, IL 60611-3008 11 E-mail address: [email protected] 12 Phone: (312) 503-0530 13 Fax: (312) 503-7912 14 15 1 bioRxiv preprint doi: https://doi.org/10.1101/251405; this version posted January 22, 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. 16 ABSTRACT 17 Intermediate filaments (IFs) are a major component of the cytoskeleton that regulates a wide 18 range of physiological properties in eukaryotic cells. In motile cells, the IF network has to adapt 19 to constant changes of cell shape and tension. In this study, we used two cell lines that express 20 vimentin and keratins 8/18 to study the dynamic behavior of these IFs.