0000000000054677

AUTHOR

Adem Yildirim

showing 3 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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SANS (USH1G) Molecularly Links the Human Usher Syndrome Protein Network to the Intraflagellar Transport Module by Direct Binding to IFT-B Proteins.

2019

The human Usher syndrome (USH) is a retinal ciliopathy, characterized by profound congenital deafness, variable vestibular dysfunction and pre-pubertal onset of retinitis pigmentosa. In the effected sensory cells, USH protein networks are assumed to function in ciliary transport processes. The USH1G protein SANS is a scaffold of the ciliary/periciliary USH protein network of photoreceptor cells. Moreover, SANS is associated with microtubules, the transport routes for protein delivery toward the cilium. To enlighten the role of SANS in ciliary transport processes, we aimed to identify transport related proteins associated with SANS. The intraflagellar transport (IFT) system is a conserved me…

0301 basic medicineciliary transportIFTPhotoreceptor cell570 Life sciences03 medical and health sciencesCell and Developmental Biology0302 clinical medicineprimary ciliaMicrotubuleIntraflagellar transportRetinitis pigmentosamedicinephotoreceptor celllcsh:QH301-705.5USH interactomeOriginal ResearchChemistryCiliumCell Biologymedicine.diseaseCell biologyCiliopathy030104 developmental biologymedicine.anatomical_structureciliopathylcsh:Biology (General)030220 oncology & carcinogenesisUSH1GAnkyrin repeatsense organsCiliary baseUsher syndrome570 BiowissenschaftenDevelopmental BiologyFrontiers in cell and developmental biology
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SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes

2021

Abstract Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome—the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal sub-complexes such as SF3B1 and the large splicing cofact…

ProteomicsAcademicSubjects/SCI00010Ribonucleoprotein U4-U6 Small NuclearSF3B1 GeneMass Spectrometry0302 clinical medicineRNA Small NuclearRNA PrecursorsIn Situ Hybridization FluorescenceRibonucleoprotein0303 health sciencesChemistryRibonucleoproteins Small NuclearImmunohistochemistryCell biologyDNA-Binding Proteinsmedicine.anatomical_structureGene Knockdown TechniquesRNA splicingRNA Splicing FactorsUsher SyndromesSpliceosomeCoiled BodiesNerve Tissue ProteinsBiologyMinor Histocompatibility Antigens03 medical and health sciencesMicroscopy Electron TransmissionRNA and RNA-protein complexesGeneticsmedicineHumanssnRNPEye ProteinsGeneCell Proliferation030304 developmental biologyCell NucleusRNAmedicine.diseasePhosphoproteinsCiliopathyAlternative SplicingCell nucleusHEK293 CellsCajal bodyCytoplasmSpliceosomesNucleus030217 neurology & neurosurgeryTranscription FactorsNucleic Acids Research
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