0000000000054684

AUTHOR

Sylvia E. C. Van Beersum

showing 4 related works from this author

PCARE and WASF3 regulate ciliary F-actin assembly that is required for the initiation of photoreceptor outer segment disk formation

2020

Significance The photoreceptor outer segments are primary cilia, modified for phototransduction by incorporation of stacked opsin-loaded membrane disks that are continuously regenerated. This process is disrupted in several types of inherited retinal dystrophy, but the driving force remained unclear. We show that C2orf71/PCARE (photoreceptor cilium actin regulator), associated with inherited retinal dystrophy subtype RP54, efficiently recruits the Arp2/3 complex activator WASF3 to the cilium. This activates an actin dynamics-driven expansion of the ciliary tip, resembling membrane evagination in lamellipodia formation. Colocalization of this actin dynamics module to the base of the outer se…

ciliummacromolecular substancesSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Actin-Related Protein 2-3 Complexchemistry.chemical_compoundMiceAll institutes and research themes of the Radboud University Medical Centerretinitis pigmentosaRetinitis pigmentosamedicineGeneticsAnimalsHumansCiliaRNA Small InterferingCiliary tipEye ProteinsCiliary membraneActinMice KnockoutMultidisciplinaryCiliumouter segmentsRetinalBiological Sciencesmedicine.diseaseRod Cell Outer SegmentPhotoreceptor outer segmentphotoreceptorActinsCell biologyWiskott-Aldrich Syndrome Protein FamilyDisease Models AnimalRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]chemistryPNAS PlusGene Expression RegulationRetinal Cone Photoreceptor Cellssense organsactinCone-Rod DystrophiesVisual phototransductionProceedings of the National Academy of Sciences USA
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Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis

2007

Contains fulltext : 53618.pdf (Publisher’s version ) (Closed access) Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photore…

MaleCandidate geneGenetics and epigenetic pathways of disease [NCMLS 6]genetic structuresMolecular Sequence DataOptic Atrophy Hereditary LeberNeuroinformatics [DCN 3]Biologymedicine.disease_causeCiliopathiesJoubert syndromeCell LineFrameshift mutationGenomic disorders and inherited multi-system disorders [IGMD 3]MiceTranslational research [ONCOL 3]Chlorocebus aethiopsPerception and Action [DCN 1]GeneticsmedicineNeurosensory disorders [UMCN 3.3]AnimalsHumansCiliaRats WistarEye ProteinsFrameshift MutationRenal disorder [IGMD 9]GeneticsMutationCiliumDisease gene identificationmedicine.diseasePhenotypeeye diseasesPedigreeRatsMice Inbred C57BLGenetic defects of metabolism [UMCN 5.1]Codon NonsenseCOS CellsFemalesense organsFunctional Neurogenomics [DCN 2]Microtubule-Associated ProteinsNature Genetics
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CiliaCarta: An integrated and validated compendium of ciliary genes

2019

The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcriptomic and evolutionary data and systematically integrated these using Bayesian statistics into a predictive score for ciliary function. This resulted in 285 candidate ciliary genes. We generated independent experimental evidence of ciliary associations for 24 out of 36 analyzed candidate proteins using multiple cell and animal model systems (mouse…

ProteomicsSensory ReceptorsNematodaSocial SciencesCiliopathiesBiochemistrySensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Transcriptome0302 clinical medicineAnimal CellsPsychologyRETINAL PHOTORECEPTOR CELLSExomeNeurons0303 health sciences030302 biochemistry & molecular biologyEukaryotaGenomicsPRIMARY CILIUMthecilium3. Good healthNucleic acidsGenetic interferenceOsteichthyesMedicineEpigeneticsCellular Structures and OrganellesCellular Typesproteomic databasesSensory Receptor CellsScienceeducationCiliary genesLEBER CONGENITAL AMAUROSISGenomics03 medical and health sciencesGeneticsCiliaCaenorhabditis elegansIDENTIFICATIONMUTATIONSEmbryosciliaOrganismsBiology and Life SciencesBayes TheoremMolecular Sequence Annotationmedicine.diseaseInvertebratesFishciliary proteomeAnimal StudiesCaenorhabditisGene expressionembryos030217 neurology & neurosurgeryDevelopmental BiologyNeurosciencePhotoreceptorsCandidate geneEmbryologyOligonucleotidesMorpholinoDatabase and Informatics MethodsRNA interferenceBayesian classifierTRANSITION ZONEZebrafishAntisense OligonucleotidesZebrafishGeneticsMultidisciplinarySpectrometric Identification of ProteinsProteomic DatabasesNucleotidesCiliumQStable Isotope Labeling by Amino Acids in Cell CultureRphotoreceptorsMetabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]Animal ModelsPhenotypeINTRAFLAGELLAR TRANSPORTDIFFERENTIATIONPhenotypeExperimental Organism SystemsCaenorhabditis ElegansVertebratesSensory PerceptionResearch ArticleSignal TransductionEXPRESSIONStable isotope labeling by amino acids in cell cultureComputational biologyBiologyResearch and Analysis MethodsSOLUTE-CARRIER-PROTEINModel OrganismsmedicineAnimalsdata integration030304 developmental biologyAfferent NeuronsReproducibility of ResultsCell Biologyzebrafishbiology.organism_classificationCiliopathyRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]Biological DatabasesCellular NeuroscienceRNAOSCP1CiliaCartaPLoS ONE
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Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.

2007

Peters, T.A./0000-0001-8443-5500; van Beersum, Sylvia E.C./0000-0002-4552-2908; Cremers, Frans/0000-0002-4954-5592; Roepman, Ronald/0000-0002-5178-8163 WOS: 000247619800019 PubMed: 17558407 Protein- protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis ( NPHP), Leber congenital amaurosis, Senior- Loken syndrome ( SLSN) or Joubert syndrome ( JBTS)(1-6). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1- like protein ( RPGRIP1L) is a homolog of RPGRIP1 ( RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis(7,8). We show t…

AdultMaleHealth aging / healthy living [IGMD 5]Eye DiseasesGenetics and epigenetic pathways of disease [NCMLS 6]TMEM67Molecular Sequence DataMembrane transport and intracellular motility [NCMLS 5]Biologymedicine.disease_causeJoubert syndromeCell LineGenomic disorders and inherited multi-system disorders [IGMD 3]NephronophthisisCerebellar DiseasesGeneticsmedicinePerception and Action [DCN 1]Basal bodyAnimalsHumansNeurosensory disorders [UMCN 3.3]CiliaAdaptor Proteins Signal TransducingRenal disorder [IGMD 9]GeneticsMutationCiliumCiliary transition zoneProteinsSyndromemedicine.diseasePedigreeRatsCytoskeletal ProteinsGenetic defects of metabolism [UMCN 5.1]RPGRIP1LFemaleKidney DiseasesFunctional Neurogenomics [DCN 2]Ciliary Motility Disorders
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