Autophagy and Regulation of Cilia Function and Assembly
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The Connections of Wnt Pathway Components with Cell Cycle and Centrosome: Side Effects Or a Hidden Logic?
Critical Reviews in Biochemistry and Molecular Biology ISSN: 1040-9238 (Print) 1549-7798 (Online) Journal homepage: http://www.tandfonline.com/loi/ibmg20 The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic? Vítězslav Bryja , Igor Červenka & Lukáš Čajánek To cite this article: Vítězslav Bryja , Igor Červenka & Lukáš Čajánek (2017): The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic?, Critical Reviews in Biochemistry and Molecular Biology, DOI: 10.1080/10409238.2017.1350135 To link to this article: http://dx.doi.org/10.1080/10409238.2017.1350135 Published online: 25 Jul 2017. Submit your article to this journal Article views: 72 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ibmg20 Download by: [Masarykova Univerzita v Brne], [Lukas Cajanek] Date: 08 August 2017, At: 01:58 CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2017 https://doi.org/10.1080/10409238.2017.1350135 REVIEW ARTICLE The connections of Wnt pathway components with cell cycle and centrosome: side effects or a hidden logic? Vıtezslav Bryjaa , Igor Cervenka b and Lukas Caj anekc aDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; bMolecular and Cellular Exercise Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; cDepartment of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic ABSTRACT ARTICLE HISTORY Wnt signaling cascade has developed together with multicellularity to orchestrate the develop- Received 10 April 2017 ment and homeostasis of complex structures. -
Educational Paper Ciliopathies
Eur J Pediatr (2012) 171:1285–1300 DOI 10.1007/s00431-011-1553-z REVIEW Educational paper Ciliopathies Carsten Bergmann Received: 11 June 2011 /Accepted: 3 August 2011 /Published online: 7 September 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Cilia are antenna-like organelles found on the (NPHP) . Ivemark syndrome . Meckel syndrome (MKS) . surface of most cells. They transduce molecular signals Joubert syndrome (JBTS) . Bardet–Biedl syndrome (BBS) . and facilitate interactions between cells and their Alstrom syndrome . Short-rib polydactyly syndromes . environment. Ciliary dysfunction has been shown to Jeune syndrome (ATD) . Ellis-van Crefeld syndrome (EVC) . underlie a broad range of overlapping, clinically and Sensenbrenner syndrome . Primary ciliary dyskinesia genetically heterogeneous phenotypes, collectively (Kartagener syndrome) . von Hippel-Lindau (VHL) . termed ciliopathies. Literally, all organs can be affected. Tuberous sclerosis (TSC) . Oligogenic inheritance . Modifier. Frequent cilia-related manifestations are (poly)cystic Mutational load kidney disease, retinal degeneration, situs inversus, cardiac defects, polydactyly, other skeletal abnormalities, and defects of the central and peripheral nervous Introduction system, occurring either isolated or as part of syn- dromes. Characterization of ciliopathies and the decisive Defective cellular organelles such as mitochondria, perox- role of primary cilia in signal transduction and cell isomes, and lysosomes are well-known -
Ciliopathiesneuromuscularciliopathies Disorders Disorders Ciliopathiesciliopathies
NeuromuscularCiliopathiesNeuromuscularCiliopathies Disorders Disorders CiliopathiesCiliopathies AboutAbout EGL EGL Genet Geneticsics EGLEGL Genetics Genetics specializes specializes in ingenetic genetic diagnostic diagnostic testing, testing, with with ne nearlyarly 50 50 years years of of clinical clinical experience experience and and board-certified board-certified labor laboratoryatory directorsdirectors and and genetic genetic counselors counselors reporting reporting out out cases. cases. EGL EGL Genet Geneticsics offers offers a combineda combined 1000 1000 molecular molecular genetics, genetics, biochemical biochemical genetics,genetics, and and cytogenetics cytogenetics tests tests under under one one roof roof and and custom custom test testinging for for all all medically medically relevant relevant genes, genes, for for domestic domestic andand international international clients. clients. EquallyEqually important important to to improving improving patient patient care care through through quality quality genetic genetic testing testing is is the the contribution contribution EGL EGL Genetics Genetics makes makes back back to to thethe scientific scientific and and medical medical communities. communities. EGL EGL Genetics Genetics is is one one of of only only a afew few clinical clinical diagnostic diagnostic laboratories laboratories to to openly openly share share data data withwith the the NCBI NCBI freely freely available available public public database database ClinVar ClinVar (>35,000 (>35,000 variants variants on on >1700 >1700 genes) genes) and and is isalso also the the only only laboratory laboratory with with a a frefree oen olinnlein dea dtabtaabsaes (eE m(EVmCVlaCslas)s,s f)e, afetuatruinrgin ag vaa vraiarniatn ctl acslasisfiscifiactiaotino sne saercahrc ahn adn rde rpeoprot rrte rqeuqeuset sint tinetrefarcfaec, ew, hwichhic fha cfailcitialiteatse rsa praidp id interactiveinteractive curation curation and and reporting reporting of of variants. -
Hydroxylation of the Eukaryotic Ribosomal Decoding Center Affects Translational Accuracy
Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy Christoph Loenarza,1, Rok Sekirnika,2, Armin Thalhammera,2, Wei Gea, Ekaterina Spivakovskya, Mukram M. Mackeena,b,3, Michael A. McDonougha, Matthew E. Cockmanc, Benedikt M. Kesslerb, Peter J. Ratcliffec, Alexander Wolfa,4, and Christopher J. Schofielda,1 aChemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford OX1 3TA, United Kingdom; bTarget Discovery Institute, University of Oxford, Oxford OX3 7FZ, United Kingdom; and cCentre for Cellular and Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom Edited by William G. Kaelin, Jr., Harvard Medical School, Boston, MA, and approved January 24, 2014 (received for review July 31, 2013) The mechanisms by which gene expression is regulated by oxygen Enzyme-catalyzed hydroxylation of intracellularly localized are of considerable interest from basic science and therapeutic proteins was once thought to be rare, but accumulating recent perspectives. Using mass spectrometric analyses of Saccharomyces evidence suggests it is widespread (11). Motivated by these cerevisiae ribosomes, we found that the amino acid residue in findings, we investigated whether the translation of mRNA to closest proximity to the decoding center, Pro-64 of the 40S subunit protein is affected by oxygen-dependent modifications. A rapidly ribosomal protein Rps23p (RPS23 Pro-62 in humans) undergoes growing eukaryotic cell devotes most of its resources to the tran- posttranslational hydroxylation. We identify RPS23 hydroxylases scription, splicing, and transport of ribosomal proteins and rRNA as a highly conserved eukaryotic subfamily of Fe(II) and 2-oxoglu- (12). We therefore reasoned that ribosomal modification is a tarate dependent oxygenases; their catalytic domain is closely re- candidate mechanism for the regulation of protein expression. -
TRIM32 Is an E3 Ubiquitin Ligase for Dysbindin
Human Molecular Genetics, 2009, Vol. 18, No. 13 2344–2358 doi:10.1093/hmg/ddp167 Advance Access published on April 6, 2009 TRIM32 is an E3 ubiquitin ligase for dysbindin Matthew Locke1,2, Caroline L. Tinsley1, Matthew A. Benson2,{ and Derek J. Blake1,Ã 1Department of Psychological Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, CF14 4XN, UK and 2Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK Received December 15, 2008; Revised and Accepted April 2, 2009 Mutations in the gene encoding tripartite motif protein 32 (TRIM32) cause two seemingly diverse diseases: limb-girdle muscular dystrophy type 2H (LGMD2H) or sarcotubular myopathy (STM) and Bardet–Biedl syndrome type 11(BBS11). Although TRIM32 is involved in protein ubiquitination, its substrates and the molecular consequences of disease-causing mutations are poorly understood. In this paper, we show that Downloaded from TRIM32 is a widely expressed ubiquitin ligase that is localized to the Z-line in skeletal muscle. Using the yeast two-hybrid system, we found that TRIM32 binds and ubiquitinates dysbindin, a protein implicated in the genetic aetiology of schizophrenia, augmenting its degradation. Small-interfering RNA-mediated knock-down of TRIM32 in myoblasts resulted in elevated levels of dysbindin. Importantly, the LGMD2H/ STM-associated TRIM32 mutations, D487N and R394H impair ubiquitin ligase activity towards dysbindin http://hmg.oxfordjournals.org/ and were mislocalized in heterologous cells. These mutants were able to self-associate and also co-immuno- precipitated with wild-type TRIM32 in transfected cells. Furthermore, the D487N mutant could bind to both dysbindin and its E2 enzyme but was defective in monoubiquitination. -
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. -
Splicing-Correcting Therapeutic Approaches for Retinal Dystrophies: Where Endogenous Gene Regulation and Specificity Matter
New Developments Splicing-Correcting Therapeutic Approaches for Retinal Dystrophies: Where Endogenous Gene Regulation and Specificity Matter Niccolo` Bacchi,1 Simona Casarosa,1,2 and Michela A. Denti1,3 1Centre for Integrative Biology (CIBIO) - University of Trento, Trento, Italy 2Neuroscience Institute - National Research Council (CNR), Pisa, Italy 3Neuroscience Institute - National Research Council (CNR), Padova, Italy Correspondence: Simona Casarosa, Splicing is an important and highly regulated step in gene expression. The ability to modulate Centre for Integrative Biology it can offer a therapeutic option for many genetic disorders. Antisense-mediated splicing- (CIBIO) - University of Trento, Via correction approaches have recently been successfully exploited for some genetic diseases, Sommarive 9, 38123 Trento, Italy; and are currently demonstrating safety and efficacy in different clinical trials. Their [email protected]. application for the treatment of retinal dystrophies could potentially solve a vast panel of Michela A. Denti, Centre for Inte- grative Biology (CIBIO) - University cases, as illustrated by the abundance of mutations that could be targeted and the versatility of ofTrento,ViaSommarive9,38123 the technique. In this review, we will give an insight of the different therapeutic strategies, Trento, Italy; focusing on the current status of their application for retinal dystrophies. [email protected]. Keywords: splicing correction, antisense oligonucleotides, retinal dystrophy, gene therapy SC and MAD contributed equally to the work presented here and should therefore be regarded as equivalent authors. Submitted: April 8, 2014 Accepted: April 11, 2014 Citation: Bacchi N, Casarosa S, Denti MA. Splicing-correcting therapeutic approaches for retinal dystrophies: where endogenous gene regulation and specificity matter. Invest Oph- thalmol Vis Sci. -
SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling
SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling Airik, Rannar; Schueler, Markus; Airik, Merlin; Cho, Jang; Ulanowicz, Kelsey A; Porath, Jonathan D; Hurd, Toby W; Bekker-Jensen, Simon; Schrøder, Jacob Morville; Andersen, Jens S.; Hildebrandt, Friedhelm Published in: P L o S One DOI: 10.1371/journal.pone.0156081 Publication date: 2016 Document version Publisher's PDF, also known as Version of record Document license: CC BY Citation for published version (APA): Airik, R., Schueler, M., Airik, M., Cho, J., Ulanowicz, K. A., Porath, J. D., Hurd, T. W., Bekker-Jensen, S., Schrøder, J. M., Andersen, J. S., & Hildebrandt, F. (2016). SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling. P L o S One, 11(5), [e0156081]. https://doi.org/10.1371/journal.pone.0156081 Download date: 04. Oct. 2021 RESEARCH ARTICLE SDCCAG8 Interacts with RAB Effector Proteins RABEP2 and ERC1 and Is Required for Hedgehog Signaling Rannar Airik1¤‡*, Markus Schueler1, Merlin Airik1, Jang Cho1, Kelsey A. Ulanowicz2, Jonathan D. Porath1, Toby W. Hurd3, Simon Bekker-Jensen4, Jacob M. Schrøder5, Jens S. Andersen5, Friedhelm Hildebrandt1,6‡* 1 Department of Medicine, Division of Nephrology, Boston Children’s Hospital, Boston, Massachusetts, United States of America, 2 Department of Pediatrics, Division of Nephrology, Children’s Hospital of a11111 Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America, 3 Medical Research Council Human Genetics Unit, Institute of -
Ciliopathies Gene Panel
Ciliopathies Gene Panel Contact details Introduction Regional Genetics Service The ciliopathies are a heterogeneous group of conditions with considerable phenotypic overlap. Levels 4-6, Barclay House These inherited diseases are caused by defects in cilia; hair-like projections present on most 37 Queen Square cells, with roles in key human developmental processes via their motility and signalling functions. Ciliopathies are often lethal and multiple organ systems are affected. Ciliopathies are London, WC1N 3BH united in being genetically heterogeneous conditions and the different subtypes can share T +44 (0) 20 7762 6888 many clinical features, predominantly cystic kidney disease, but also retinal, respiratory, F +44 (0) 20 7813 8578 skeletal, hepatic and neurological defects in addition to metabolic defects, laterality defects and polydactyly. Their clinical variability can make ciliopathies hard to recognise, reflecting the ubiquity of cilia. Gene panels currently offer the best solution to tackling analysis of genetically Samples required heterogeneous conditions such as the ciliopathies. Ciliopathies affect approximately 1:2,000 5ml venous blood in plastic EDTA births. bottles (>1ml from neonates) Ciliopathies are generally inherited in an autosomal recessive manner, with some autosomal Prenatal testing must be arranged dominant and X-linked exceptions. in advance, through a Clinical Genetics department if possible. Referrals Amniotic fluid or CV samples Patients presenting with a ciliopathy; due to the phenotypic variability this could be a diverse set should be sent to Cytogenetics for of features. For guidance contact the laboratory or Dr Hannah Mitchison dissecting and culturing, with ([email protected]) / Prof Phil Beales ([email protected]) instructions to forward the sample to the Regional Molecular Genetics Referrals will be accepted from clinical geneticists and consultants in nephrology, metabolic, laboratory for analysis respiratory and retinal diseases. -
The Role of Primary Cilia in the Crosstalk Between the Ubiquitin–Proteasome System and Autophagy
cells Review The Role of Primary Cilia in the Crosstalk between the Ubiquitin–Proteasome System and Autophagy Antonia Wiegering, Ulrich Rüther and Christoph Gerhardt * Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, 40225 Düsseldorf, Germany; [email protected] (A.W.); [email protected] (U.R.) * Correspondence: [email protected]; Tel.: +49-(0)211-81-12236 Received: 29 December 2018; Accepted: 11 March 2019; Published: 14 March 2019 Abstract: Protein degradation is a pivotal process for eukaryotic development and homeostasis. The majority of proteins are degraded by the ubiquitin–proteasome system and by autophagy. Recent studies describe a crosstalk between these two main eukaryotic degradation systems which allows for establishing a kind of safety mechanism. If one of these degradation systems is hampered, the other compensates for this defect. The mechanism behind this crosstalk is poorly understood. Novel studies suggest that primary cilia, little cellular protrusions, are involved in the regulation of the crosstalk between the two degradation systems. In this review article, we summarise the current knowledge about the association between cilia, the ubiquitin–proteasome system and autophagy. Keywords: protein aggregation; neurodegenerative diseases; OFD1; BBS4; RPGRIP1L; hedgehog; mTOR; IFT; GLI 1. Introduction Protein aggregates are huge protein accumulations that develop as a consequence of misfolded proteins. The occurrence of protein aggregates is associated with the development of neurodegenerative diseases, such as Huntington’s disease, prion disorders, Alzheimer’s disease and Parkinson’s disease [1–3], demonstrating that the degradation of incorrectly folded proteins is of eminent importance for human health. In addition to the destruction of useless and dangerous proteins (protein quality control), protein degradation is an important process to regulate the cell cycle, to govern transcription and also to control intra- and intercellular signal transduction [4–6]. -
Intraflagellar Transport Proteins Are Essential for Cilia Formation and for Planar Cell Polarity
BASIC RESEARCH www.jasn.org Intraflagellar Transport Proteins Are Essential for Cilia Formation and for Planar Cell Polarity Ying Cao, Alice Park, and Zhaoxia Sun Department of Genetics, Yale University School of Medicine, New Haven, Connecticut ABSTRACT The highly conserved intraflagellar transport (IFT) proteins are essential for cilia formation in multiple organisms, but surprisingly, cilia form in multiple zebrafish ift mutants. Here, we detected maternal deposition of ift gene products in zebrafish and found that ciliary assembly occurs only during early developmental stages, supporting the idea that maternal contribution of ift gene products masks the function of IFT proteins during initial development. In addition, the basal bodies in multiciliated cells of the pronephric duct in ift mutants were disorganized, with a pattern suggestive of defective planar cell polarity (PCP). Depletion of pk1, a core PCP component, similarly led to kidney cyst formation and basal body disorganization. Furthermore, we found that multiple ift genes genetically interact with pk1. Taken together, these data suggest that IFT proteins play a conserved role in cilia formation and planar cell polarity in zebrafish. J Am Soc Nephrol 21: 1326–1333, 2010. doi: 10.1681/ASN.2009091001 The cilium is a cell surface organelle that is almost In zebrafish, mutants of ift57, ift81, ift88, and ubiquitously present on vertebrate cells. Pro- ift172 have numerous defects commonly associated truding from the cell into its environment, the with ciliary abnormalities.13,14 -
Kif9 Is an Active Kinesin Motor Required for Ciliary Beating and Proximodistal Patterning of Motile Axonemes
bioRxiv preprint doi: https://doi.org/10.1101/2021.08.26.457815; this version posted August 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes Mia J. Konjikusic1,2,3, Chanjae Lee1, Yang Yue4, Bikram D. Shrestha5, Ange M. Nguimtsop1, Amjad Horani6, Steven Brody7,8, Vivek N. Prakash5,9, Ryan S. Gray2,3, Kristen J. Verhey4, John B. Wallingford1* 1 Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA. 2 Department of Pediatrics, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd, The University of Texas at Austin, Dell Medical School, Austin, TX, USA. 3 Department of Nutritional Sciences, 200 W 24th Street, The University of Texas at Austin, Austin, TX 78712, USA. 4 Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. 5 Department of Physics, University of Miami, Coral Gables, FL, USA. 6 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA. 7 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. 8 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 63110 USA 9 Department of Biology and Department of Marine Biology and Ecology, University of Miami, Coral Gables, FL, USA. *Corresponding Author [email protected] Patterson Labs 2401 Speedway Austin, Tx 78712 bioRxiv preprint doi: https://doi.org/10.1101/2021.08.26.457815; this version posted August 27, 2021.