Ciliary Transcription Factors and Mirnas Precisely Regulate Cp110
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Mutations in CDK5RAP2 Cause Seckel Syndrome Go¨ Khan Yigit1,2,3,A, Karen E
ORIGINAL ARTICLE Mutations in CDK5RAP2 cause Seckel syndrome Go¨ khan Yigit1,2,3,a, Karen E. Brown4,a,Hu¨ lya Kayserili5, Esther Pohl1,2,3, Almuth Caliebe6, Diana Zahnleiter7, Elisabeth Rosser8, Nina Bo¨ gershausen1,2,3, Zehra Oya Uyguner5, Umut Altunoglu5, Gudrun Nu¨ rnberg2,3,9, Peter Nu¨ rnberg2,3,9, Anita Rauch10, Yun Li1,2,3, Christian Thomas Thiel7 & Bernd Wollnik1,2,3 1Institute of Human Genetics, University of Cologne, Cologne, Germany 2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany 3Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany 4Chromosome Biology Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN, UK 5Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey 6Institute of Human Genetics, Christian-Albrechts-University of Kiel, Kiel, Germany 7Institute of Human Genetics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany 8Department of Clinical Genetics, Great Ormond Street Hospital for Children, London, WC1N 3EH, UK 9Cologne Center for Genomics, University of Cologne, Cologne, Germany 10Institute of Medical Genetics, University of Zurich, Schwerzenbach-Zurich, Switzerland Keywords Abstract CDK5RAP2, CEP215, microcephaly, primordial dwarfism, Seckel syndrome Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by pre- natal proportionate short stature, severe microcephaly, intellectual disability, and Correspondence characteristic facial features. Here, we describe the novel homozygous splice-site Bernd Wollnik, Center for Molecular mutations c.383+1G>C and c.4005-9A>GinCDK5RAP2 in two consanguineous Medicine Cologne (CMMC) and Institute of families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a centrosomal pro- Human Genetics, University of Cologne, tein which is known to be essential for centrosomal cohesion and proper spindle Kerpener Str. -
Supplemental Information Proximity Interactions Among Centrosome
Current Biology, Volume 24 Supplemental Information Proximity Interactions among Centrosome Components Identify Regulators of Centriole Duplication Elif Nur Firat-Karalar, Navin Rauniyar, John R. Yates III, and Tim Stearns Figure S1 A Myc Streptavidin -tubulin Merge Myc Streptavidin -tubulin Merge BirA*-PLK4 BirA*-CEP63 BirA*- CEP192 BirA*- CEP152 - BirA*-CCDC67 BirA* CEP152 CPAP BirA*- B C Streptavidin PCM1 Merge Myc-BirA* -CEP63 PCM1 -tubulin Merge BirA*- CEP63 DMSO - BirA* CEP63 nocodazole BirA*- CCDC67 Figure S2 A GFP – + – + GFP-CEP152 + – + – Myc-CDK5RAP2 + + + + (225 kDa) Myc-CDK5RAP2 (216 kDa) GFP-CEP152 (27 kDa) GFP Input (5%) IP: GFP B GFP-CEP152 truncation proteins Inputs (5%) IP: GFP kDa 1-7481-10441-1290218-1654749-16541045-16541-7481-10441-1290218-1654749-16541045-1654 250- Myc-CDK5RAP2 150- 150- 100- 75- GFP-CEP152 Figure S3 A B CEP63 – – + – – + GFP CCDC14 KIAA0753 Centrosome + – – + – – GFP-CCDC14 CEP152 binding binding binding targeting – + – – + – GFP-KIAA0753 GFP-KIAA0753 (140 kDa) 1-496 N M C 150- 100- GFP-CCDC14 (115 kDa) 1-424 N M – 136-496 M C – 50- CEP63 (63 kDa) 1-135 N – 37- GFP (27 kDa) 136-424 M – kDa 425-496 C – – Inputs (2%) IP: GFP C GFP-CEP63 truncation proteins D GFP-CEP63 truncation proteins Inputs (5%) IP: GFP Inputs (5%) IP: GFP kDa kDa 1-135136-424425-4961-424136-496FL Ctl 1-135136-424425-4961-424136-496FL Ctl 1-135136-424425-4961-424136-496FL Ctl 1-135136-424425-4961-424136-496FL Ctl Myc- 150- Myc- 100- CCDC14 KIAA0753 100- 100- 75- 75- GFP- GFP- 50- CEP63 50- CEP63 37- 37- Figure S4 A siCtl -
Renal Cell Neoplasms Contain Shared Tumor Type–Specific Copy Number Variations
The American Journal of Pathology, Vol. 180, No. 6, June 2012 Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajpath.2012.01.044 Tumorigenesis and Neoplastic Progression Renal Cell Neoplasms Contain Shared Tumor Type–Specific Copy Number Variations John M. Krill-Burger,* Maureen A. Lyons,*† The annual incidence of renal cell carcinoma (RCC) has Lori A. Kelly,*† Christin M. Sciulli,*† increased steadily in the United States for the past three Patricia Petrosko,*† Uma R. Chandran,†‡ decades, with approximately 58,000 new cases diag- 1,2 Michael D. Kubal,§ Sheldon I. Bastacky,*† nosed in 2010, representing 3% of all malignancies. Anil V. Parwani,*†‡ Rajiv Dhir,*†‡ and Treatment of RCC is complicated by the fact that it is not a single disease but composes multiple tumor types with William A. LaFramboise*†‡ different morphological characteristics, clinical courses, From the Departments of Pathology* and Biomedical and outcomes (ie, clear-cell carcinoma, 82% of RCC ‡ Informatics, University of Pittsburgh, Pittsburgh, Pennsylvania; cases; type 1 or 2 papillary tumors, 11% of RCC cases; † the University of Pittsburgh Cancer Institute, Pittsburgh, chromophobe tumors, 5% of RCC cases; and collecting § Pennsylvania; and Life Technologies, Carlsbad, California duct carcinoma, approximately 1% of RCC cases).2,3 Benign renal neoplasms are subdivided into papillary adenoma, renal oncocytoma, and metanephric ade- Copy number variant (CNV) analysis was performed on noma.2,3 Treatment of RCC often involves surgical resec- renal cell carcinoma (RCC) specimens (chromophobe, tion of a large renal tissue component or removal of the clear cell, oncocytoma, papillary type 1, and papillary entire affected kidney because of the relatively large size of type 2) using high-resolution arrays (1.85 million renal tumors on discovery and the availability of a life-sus- probes). -
Anatomy of the Axon
Anatomy of the Axon: Dissecting the role of microtubule plus-end tracking proteins in axons of hippocampal neurons ISBN: 978-90-393-7095-7 On the cover: Interpretation of Rembrandt van Rijn’s iconic oil painting The Anatomy Lesson of Dr. Nicolaes Tulp (1632). Instead of a human subject, a neuron is being dissected under the watchful eye of members of the Hoogenraad & Akhmanova labs circa 2018. The doctoral candidate takes on the role of Dr. Nicolaes Tulp. The year in which this thesis is published, 2019, marks the 350th anniversary of Rembrandt’s passing. It is therefore declared Year of Rembrandt. Cover photography: Jasper Landman (Bob & Fzbl Photography) Design and layout: Dieudonnée van de Willige © 2019; CC-BY-NC-ND. Printed in The Netherlands. Anatomy of the Axon: Dissecting the role of microtubule plus-end tracking proteins in axons of hippocampal neurons Anatomie van de Axon: Ontleding van de rol van microtubulus-plus-eind-bindende eiwitten in axonen van hippocampale neuronen (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. H.R.B.M. Kummeling, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op woensdag 22 mei 2019 des middags te 2.30 uur door Dieudonnée van de Willige geboren op 24 oktober 1990 te Antwerpen, België Promotoren: Prof. dr. C.C. Hoogenraad Prof. dr. A. Akhmanova Voor Hans & Miranda Index Preface 7 List of non-standard abbreviations 9 Microtubule plus-end tracking proteins -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Centrin2 Regulates CP110 Removal in Primary Cilium Formation
Published March 9, 2015 JCB: Report Centrin2 regulates CP110 removal in primary cilium formation Suzanna L. Prosser and Ciaran G. Morrison Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland rimary cilia are antenna-like sensory microtubule ciliogenesis in chicken DT40 B lymphocytes required cen- structures that extend from basal bodies, plasma trin2. We disrupted CETN2 in human retinal pigmented P membrane–docked mother centrioles. Cellular qui- epithelial cells, and despite having intact centrioles, they escence potentiates ciliogenesis, but the regulation of basal were unable to make cilia upon serum starvation, show- body formation is not fully understood. We used reverse ing abnormal localization of distal appendage proteins genetics to test the role of the small calcium-binding pro- and failing to remove the ciliation inhibitor CP110. Knock- tein, centrin2, in ciliogenesis. Primary cilia arise in most down of CP110 rescued ciliation in CETN2-deficient cells. cell types but have not been described in lymphocytes. Thus, centrin2 regulates primary ciliogenesis through con- We show here that serum starvation of transformed, cul- trolling CP110 levels. Downloaded from tured B and T cells caused primary ciliogenesis. Efficient Introduction Primary cilia are crucial for several signal transduction path- the immune synapse, a membrane region at which cells of on April 19, 2017 ways (Goetz and Anderson, 2010). Their assembly is an or- the immune system contact their target cells, helps to estab- dered process that must be closely integrated with the cell cycle lish a specialized structure that has several similarities with cilia because of the dual roles of centrioles in ciliation and in mito- (Stinchcombe and Griffiths, 2014). -
Kinetochores Accelerate Centrosome Separation to Ensure Faithful Chromosome Segregation
906 Research Article Kinetochores accelerate centrosome separation to ensure faithful chromosome segregation Nunu Mchedlishvili1,*, Samuel Wieser1,2,*, Rene´ Holtackers1, Julien Mouysset1, Mukta Belwal1, Ana C. Amaro1 and Patrick Meraldi1,` 1Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, 8093 Zu¨rich, Switzerland 2Wellcome Trust/Cancer Research Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK *These authors contributed equally to this work `Author for correspondence ([email protected]) Accepted 28 August 2011 Journal of Cell Science 125, 906–918 ß 2012. Published by The Company of Biologists Ltd doi: 10.1242/jcs.091967 Summary At the onset of mitosis, cells need to break down their nuclear envelope, form a bipolar spindle and attach the chromosomes to microtubules via kinetochores. Previous studies have shown that spindle bipolarization can occur either before or after nuclear envelope breakdown. In the latter case, early kinetochore–microtubule attachments generate pushing forces that accelerate centrosome separation. However, until now, the physiological relevance of this prometaphase kinetochore pushing force was unknown. We investigated the depletion phenotype of the kinetochore protein CENP-L, which we find to be essential for the stability of kinetochore microtubules, for a homogenous poleward microtubule flux rate and for the kinetochore pushing force. Loss of this force in prometaphase not only delays centrosome separation by 5–6 minutes, it also causes massive chromosome alignment and segregation defects due to the formation of syntelic and merotelic kinetochore–microtubule attachments. By contrast, CENP-L depletion has no impact on mitotic progression in cells that have already separated their centrosomes at nuclear envelope breakdown. -
Profiling of Cellular Immune Responses to Mycoplasma Pulmonis Infection in C57BL/6 and DBA/2 Mice
Title Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice Author(s) Boonyarattanasoonthorn, Tussapon Citation 北海道大学. 博士(獣医学) 甲第13723号 Issue Date 2019-09-25 DOI 10.14943/doctoral.k13723 Doc URL http://hdl.handle.net/2115/76392 Type theses (doctoral) File Information Tussapon_BOONYARATTANASOONTHORN.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice (C57BL/6 マウスと DBA/2 マウスにおける Mycoplasma pulmonis 感染に対 する細胞免疫反応のプロファイリング) Tussapon Boonyarattanasoonthorn Laboratory of Laboratory Animal Science and Medicine Department of Applied Veterinary Science Graduate School of Veterinary Medicine Hokkaido University Japan ABBREVIATIONS ANOVA Analysis of variance B6 C57BL/6 (C57BL/6NCrSlc) BALF Bronchoalveolar lavage fluid b.w. Body weight CFU Colony-forming unit Chr Chromosome cM Centimorgan D2 DBA/2 (DBA/2CrSlc) d.p.i. Days post infection EDTA Ethylenediaminetetraacetic acid H&E Hematoxylin and eosin IFN- γ Interferon-gamma IL Interleukin LCs Lymphoid clusters LOD Logarithm of the odds LRS Likelihood ratio statistic Mbp Mega base pairs MFTs Mediastinal fat tissues MGI Mouse genome informatics M. pulmonis Mycoplasma pulmonis PBS Phosphate-buffered saline PCR Polymerase chain reaction QTL Quantitative trait locus SE Standard error SPF Specific pathogen-free TNF-α Tumor necrosis factor-alpha TABLE OF CONTENTS PREFACE ····································································································· -
Integrated Analysis of Gene Expression and Copy Number Variations in MET Proto‑Oncogene‑Transformed Human Primary Osteoblasts
MOLECULAR MEDICINE REPORTS 17: 2543-2548, 2018 Integrated analysis of gene expression and copy number variations in MET proto‑oncogene‑transformed human primary osteoblasts RU‑JIANG JIA*, CHUN‑GEN LAN*, XIU‑CHAO WANG and CHUN‑TAO GAO Department of Pancreatic Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China Received August 29, 2017; Accepted October 30, 2017 DOI: 10.3892/mmr.2017.8135 Abstract. The aim of the present study was to screen the domain binding protein 1-like 1, growth factor independent 1, potential osteosarcoma (OS)-associated genes and to obtain cathepsin Z, WNK lysine deficient protein kinase 1, glutathione additional insight into the pathogenesis of OS. Transcriptional S-transferase mu 2 and microsomal glutathione S-transferase 1. profile (ID: GSE28256) and copy number variations (CNV) Therefore, cell cycle-associated genes including E2F1, E2F2, profile were downloaded from Gene Expression Omnibus RB1 and CCND1, and cell adhesion-associated genes, such as database. Differentially expressed genes (DEGs) between CDH18 and LAMA1 may be used as diagnosis and/or thera- MET proto-oncogene-transformed human primary osteoblast peutic markers for patients with OS. (MET-HOB) samples and the control samples were identi- fied using the Linear Models for Microarray Data package. Introduction Subsequently, CNV areas and CNVs were identified using cut‑off criterion of >30%‑overlap within the cases using detect_cnv.pl Osteosarcoma (OS), also termed bone sarcoma, originates in PennCNV. Genes shared in DEGs and CNVs were obtained from bone and particularly from the mesenchymal stem cell and discussed. -
The Transformation of the Centrosome Into the Basal Body: Similarities and Dissimilarities Between Somatic and Male Germ Cells and Their Relevance for Male Fertility
cells Review The Transformation of the Centrosome into the Basal Body: Similarities and Dissimilarities between Somatic and Male Germ Cells and Their Relevance for Male Fertility Constanza Tapia Contreras and Sigrid Hoyer-Fender * Göttingen Center of Molecular Biosciences, Johann-Friedrich-Blumenbach Institute for Zoology and Anthropology-Developmental Biology, Faculty of Biology and Psychology, Georg-August University of Göttingen, 37077 Göttingen, Germany; [email protected] * Correspondence: [email protected] Abstract: The sperm flagellum is essential for the transport of the genetic material toward the oocyte and thus the transmission of the genetic information to the next generation. During the haploid phase of spermatogenesis, i.e., spermiogenesis, a morphological and molecular restructuring of the male germ cell, the round spermatid, takes place that includes the silencing and compaction of the nucleus, the formation of the acrosomal vesicle from the Golgi apparatus, the formation of the sperm tail, and, finally, the shedding of excessive cytoplasm. Sperm tail formation starts in the round spermatid stage when the pair of centrioles moves toward the posterior pole of the nucleus. The sperm tail, eventually, becomes located opposed to the acrosomal vesicle, which develops at the anterior pole of the nucleus. The centriole pair tightly attaches to the nucleus, forming a nuclear membrane indentation. An Citation: Tapia Contreras, C.; articular structure is formed around the centriole pair known as the connecting piece, situated in the Hoyer-Fender, S. The Transformation neck region and linking the sperm head to the tail, also named the head-to-tail coupling apparatus or, of the Centrosome into the Basal in short, HTCA. -
2014-Platform-Abstracts.Pdf
American Society of Human Genetics 64th Annual Meeting October 18–22, 2014 San Diego, CA PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Saturday 41 Statistical Methods for Population 5:30pm–6:50pm: Session 2: Plenary Abstracts Based Studies Room 20A #198–#205 Featured Presentation I (4 abstracts) Hall B1 #1–#4 42 Genome Variation and its Impact on Autism and Brain Development Room 20BC #206–#213 Sunday 43 ELSI Issues in Genetics Room 20D #214–#221 1:30pm–3:30pm: Concurrent Platform Session A (12–21): 44 Prenatal, Perinatal, and Reproductive 12 Patterns and Determinants of Genetic Genetics Room 28 #222–#229 Variation: Recombination, Mutation, 45 Advances in Defining the Molecular and Selection Hall B1 Mechanisms of Mendelian Disorders Room 29 #230–#237 #5-#12 13 Genomic Studies of Autism Room 6AB #13–#20 46 Epigenomics of Normal Populations 14 Statistical Methods for Pedigree- and Disease States Room 30 #238–#245 Based Studies Room 6CF #21–#28 15 Prostate Cancer: Expression Tuesday Informing Risk Room 6DE #29–#36 8:00pm–8:25am: 16 Variant Calling: What Makes the 47 Plenary Abstracts Featured Difference? Room 20A #37–#44 Presentation III Hall BI #246 17 New Genes, Incidental Findings and 10:30am–12:30pm:Concurrent Platform Session D (49 – 58): Unexpected Observations Revealed 49 Detailing the Parts List Using by Exome Sequencing Room 20BC #45–#52 Genomic Studies Hall B1 #247–#254 18 Type 2 Diabetes Genetics Room 20D #53–#60 50 Statistical Methods for Multigene, 19 Genomic Methods in Clinical Practice Room 28 #61–#68 Gene Interaction -
WO 2013/064702 A2 10 May 2013 (10.05.2013) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2013/064702 A2 10 May 2013 (10.05.2013) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C12Q 1/68 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/EP2012/071868 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 5 November 20 12 (05 .11.20 12) NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (25) Filing Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (26) Publication Language: English ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1118985.9 3 November 201 1 (03. 11.201 1) GB kind of regional protection available): ARIPO (BW, GH, 13/339,63 1 29 December 201 1 (29. 12.201 1) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant: DIAGENIC ASA [NO/NO]; Grenseveien 92, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, N-0663 Oslo (NO).