0000000000054678

AUTHOR

Rob W.j. Collin

showing 2 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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Zebrafish as a Model to Evaluate a CRISPR/Cas9-Based Exon Excision Approach as a Future Treatment Option for EYS-Associated Retinitis Pigmentosa

2021

Retinitis pigmentosa (RP) is an inherited retinal disease (IRD) with an overall prevalence of 1 in 4000 individuals. Mutations in EYS (Eyes shut homolog) are among the most frequent causes of non-syndromic autosomal recessively inherited RP and act via a loss-of-function mechanism. In light of the recent successes for other IRDs, we investigated the therapeutic potential of exon skipping for EYS-associated RP. CRISPR/Cas9 was employed to generate zebrafish from which the region encompassing the orthologous exons 37-41 of human EYS (eys exons 40-44) was excised from the genome. The excision of these exons was predicted to maintain the open reading frame and to result in the removal of exactl…

QH301-705.5CatalysisSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]ArticleInorganic ChemistryExonAll institutes and research themes of the Radboud University Medical CenterEYSProtein Domainsretinitis pigmentosaRetinitis pigmentosamedicineCRISPRCoding regionAnimals<i>EYS</i>Biology (General)Physical and Theoretical ChemistryOuter nuclear layerEye ProteinsQD1-999Molecular BiologyZebrafishCRISPR/Cas9SpectroscopyGeneticsexon skipping therapybiologyOrganic ChemistryphotoreceptorsGeneral MedicineExonsGenetic TherapyZebrafish Proteinsmedicine.diseasebiology.organism_classificationzebrafishExon skippingComputer Science ApplicationsChemistryOpen reading frameDisease Models Animalmedicine.anatomical_structurePhenotypeCRISPR-Cas Systemsantisense oligonucleotidesInternational Journal of Molecular Sciences
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