Search results for "usher syndrome"

showing 10 items of 56 documents

SANS (USH1G) expression in developing and mature mammalian retina

2008

AbstractThe human Usher syndrome (USH) is the most common form of combined deaf-blindness. Usher type I (USH1), the most severe form, is characterized by profound congenital deafness, constant vestibular dysfunction and prepubertal-onset of retinitis pigmentosa. Five corresponding genes of the six USH1 genes have been cloned so far. The USH1G gene encodes the SANS (scaffold protein containing ankyrin repeats and SAM domain) protein which consists of protein motifs known to mediate protein–protein interactions. Recent studies indicated SANS function as a scaffold protein in the protein interactome related to USH.Here, we generated specific antibodies for SANS protein expression analyses. Our…

Retinal degenerationScaffold proteinBlotting WesternNerve Tissue ProteinsBiologyRibbon synapseRats Inbred WKYPhotoreceptor cellRetinaMiceXenopus laevisAntibody SpecificityCiliogenesisConnecting ciliumRetinitis pigmentosamedicineAnimalsCiliaEye ProteinsCentrosomeRetinaCiliogenesisPhotoreceptor cellsCiliumImmune SeraCiliary BodyFibroblastsmedicine.diseaseSynapseSensory SystemsCell biologyRatsMice Inbred C57BLOphthalmologymedicine.anatomical_structureSynapsesRetinal developmentsense organsUsher SyndromesUsher syndromePhotoreceptor Cells VertebrateSynaptosomesVision Research
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Expression and subcellular localization of USH1C/harmonin in the human retina provide insights into pathomechanisms and therapy

2021

AbstractUsher syndrome (USH) is the most common form of hereditary deafness-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course, and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinas uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq…

Scaffold proteinGene isoformRetinabiologyUsher syndromeCiliummedicine.diseasePhenotypeCell biologymedicine.anatomical_structureRhodopsinotorhinolaryngologic diseasesmedicinebiology.proteinMuller glia
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Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2.

2005

Contains fulltext : 48386.pdf (Publisher’s version ) (Closed access) Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. USH is clinically and genetically heterogeneous with at least 11 chromosomal loci assigned to the three USH types (USH1A-G, USH2A-C, USH3A). Although the different USH types exhibit almost the same phenotype in human, the identified USH genes encode for proteins which belong to very different protein classes and families. We and others recently reported that the scaffold protein harmonin (USH1C-gene product) integrates all identified USH1 molecules in a USH1-protein network. Here, we investigated the relationship between the USH2 molecules a…

Scaffold proteinGenetics and epigenetic pathways of disease [NCMLS 6]Usher syndromeStereocilia (inner ear)Cell Cycle ProteinsBiologyInteractomeReceptors G-Protein-CoupledMiceotorhinolaryngologic diseasesGeneticsmedicineAnimalsNeurosensory disorders [UMCN 3.3]Photoreceptor CellsRats WistarMolecular BiologyGeneGenetics (clinical)Renal disorder [IGMD 9]GeneticsExtracellular Matrix ProteinsStereociliumBinding SitesHair Cells Auditory InnerSodium-Bicarbonate SymportersUsher Syndrome Type 1General Medicinemedicine.diseasePhenotypeRatsMice Inbred C57BLCytoskeletal ProteinsCarrier ProteinsUsher Syndromes
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A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells.

2008

Contains fulltext : 69178.pdf (Publisher’s version ) (Closed access) The human Usher syndrome (USH) is the most frequent cause of combined deaf-blindness. USH is genetically heterogeneous with at least 12 chromosomal loci assigned to three clinical types, USH1-3. Although these USH types exhibit similar phenotypes in human, the corresponding gene products belong to very different protein classes and families. The scaffold protein harmonin (USH1C) was shown to integrate all identified USH1 and USH2 molecules into protein networks. Here, we analyzed a protein network organized in the absence of harmonin by the scaffold proteins SANS (USH1G) and whirlin (USH2D). Immunoelectron microscopic anal…

Scaffold proteinGenetics and epigenetic pathways of disease [NCMLS 6]XenopusCell Cycle ProteinsNerve Tissue ProteinsBiologyIn Vitro TechniquesNeuroinformatics [DCN 3]TransfectionModels BiologicalReceptors G-Protein-CoupledMiceChlorocebus aethiopsProtein Interaction MappingGeneticsPerception and Action [DCN 1]otorhinolaryngologic diseasesAnimalsHumansNeurosensory disorders [UMCN 3.3]Cell Cycle ProteinMicroscopy ImmunoelectronMolecular BiologyIntegral membrane proteinGenetics (clinical)Adaptor Proteins Signal TransducingRenal disorder [IGMD 9]GeneticsMice KnockoutExtracellular Matrix ProteinsCiliumSignal transducing adaptor proteinMembrane ProteinsGeneral MedicineTransmembrane proteinCell biologyMice Inbred C57BLCytoskeletal ProteinsEctodomainGenetic defects of metabolism [UMCN 5.1]COS CellsNIH 3T3 CellsCervical collarUsher SyndromesFunctional Neurogenomics [DCN 2]Photoreceptor Cells VertebrateSubcellular FractionsImmunity infection and tissue repair [NCMLS 1]
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Usher Syndrome Protein Network Functions in the Retina and their Relation to Other Retinal Ciliopathies

2014

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically and clinically heterogeneous: 15 chromosomal loci assigned to 3 clinical types, USH1-3. All USH1 and 2 proteins are organized into protein networks by the scaffold proteins harmonin (USH1C), whirlin (USH2D) and SANS (USH1G). This has contributed essentially to our current understanding of the USH protein function in the eye and the ear and explains why defects in proteins of different families cause very similar phenotypes. Ongoing in depth analyses of USH protein networks in the eye indicated cytoskeletal functions as well as roles in molecular transport processes and ciliary…

Scaffold proteinGeneticsRetinaUsher syndromeBiologymedicine.diseaseInteractomeCiliopathiesCiliopathymedicine.anatomical_structureRetinitis pigmentosaotorhinolaryngologic diseasesmedicineRetinal Dystrophies
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Gene-based treatment options for Usher type 1C by translational read-through of a nonsense mutation

2012

The Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. The ciliopathy is clinically and genetically heterogeneous, assigned to three clinical USH types of which the most severe type is USH1. The USH1C gene encodes the PDZ containing scaffold protein harmonin which is expressed in form of numerous alternatively spliced variants. Hamonin binds directly to all USH1/2 proteins and is a key organizer of USH protein networks in photoreceptor cells. So far no effective treatment for the ophthalmic component of USH exists. Translational read-through was introduced as an innovative therapy option for several non-ocular diseases caused by nonsense mutations leading …

Scaffold proteinGeneticslcsh:CytologyUsher syndromePDZ domainNonsense mutationCell BiologyBiologymedicine.diseaseCiliopathiesPhotoreceptor cellCell biologyCiliopathymedicine.anatomical_structureotorhinolaryngologic diseasesmedicineOral Presentationlcsh:QH573-671GeneCilia
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Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-mediated endocytosis.

2014

Item does not contain fulltext The human Usher syndrome (USH) is a complex ciliopathy with at least 12 chromosomal loci assigned to three clinical subtypes, USH1-3. The heterogeneous USH proteins are organized into protein networks. Here, we identified Magi2 (membrane-associated guanylate kinase inverted-2) as a new component of the USH protein interactome, binding to the multifunctional scaffold protein SANS (USH1G). We showed that the SANS-Magi2 complex assembly is regulated by the phosphorylation of an internal PDZ-binding motif in the sterile alpha motif domain of SANS by the protein kinase CK2. We affirmed Magi2's role in receptor-mediated, clathrin-dependent endocytosis and showed tha…

Scaffold proteinGuanylate kinaseMolecular Sequence DataPrimary Cell CultureNerve Tissue ProteinsBiologyEndocytosisPhotoreceptor cellExocytosisMiceCiliogenesisGeneticsmedicineAnimalsHumansProtein Interaction Domains and MotifsAmino Acid SequencePhosphorylationRNA Small InterferingSensory disorders Radboud Institute for Molecular Life Sciences [Radboudumc 12]Molecular BiologyGenetics (clinical)Adaptor Proteins Signal TransducingBinding SitesGeneral MedicineClathrinEndocytosisCell biologyMice Inbred C57BLRenal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]medicine.anatomical_structureHEK293 CellsGene Expression RegulationCiliary pocketCarrier ProteinsSterile alpha motifGuanylate KinasesSequence AlignmentUsher SyndromesPhotoreceptor Cells VertebrateProtein BindingSignal TransductionHuman molecular genetics
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Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher …

2006

Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. It is clinically and genetically heterogeneous and at least 12 chromosomal loci are assigned to three clinical USH types, namely USH1A-G, USH2A-C, USH3A (Davenport, S.L.H., Omenn, G.S., 1977. The heterogeneity of Usher syndrome. Vth Int. Conf. Birth Defects, Montreal; Petit, C., 2001. Usher syndrome: from genetics to pathogenesis. Annu. Rev. Genomics Hum. Genet. 2, 271-297). Mutations in USH type 1 genes cause the most severe form of USH. In USH1 patients, congenital deafness is combined with a pre-pubertal onset of retinitis pigmentosa (RP) and severe vestibular dysfunctions. Those with USH2 have moderate to…

Scaffold proteinModels MolecularUsher syndromePDZ domainProtocadherinCadherin Related ProteinsCell Cycle ProteinsNerve Tissue ProteinsBiologyDeafnessMyosinsCellular and Molecular NeuroscienceRetinitis pigmentosaotorhinolaryngologic diseasesmedicineAnimalsHumansAdaptor Proteins Signal TransducingGeneticsExtracellular Matrix ProteinsModels GeneticCadherinRetinal DegenerationSignal transducing adaptor proteinDyneinsMembrane Proteinsmedicine.diseaseCadherinsSensory SystemsOphthalmologyCytoskeletal ProteinsDisease Models AnimalMembrane proteinMyosin VIIaMutationMicrotubule ProteinsVestibule LabyrinthUsher SyndromesExperimental eye research
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Direct interaction of the Usher syndrome 1G protein SANS and myomegalin in the retina

2011

Contains fulltext : 96822.pdf (Publisher’s version ) (Closed access) The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeat…

Scaffold proteinUsher syndromePhosphodiesterase 4D interacting protein (PDE4DIP)Muscle ProteinsPlasma protein bindingMice0302 clinical medicineYeastsChlorocebus aethiopsNuclear proteinCells CulturedGenetics0303 health scienceseducation.field_of_studyNuclear ProteinsCell biologyCOS CellssymbolsPhotoreceptor Cells VertebrateProtein BindingMicrotubule based transportNerve Tissue ProteinsBiologyModels BiologicalRetina03 medical and health sciencessymbols.namesakemedicineAnimalsHumanseducationMolecular BiologyAdaptor Proteins Signal Transducing030304 developmental biologyCell BiologyGlycostation disorders [IGMD 4]Golgi apparatusmedicine.diseaseMacaca mulattaMice Inbred C57BLCytoskeletal ProteinsPhotoreceptor cell functionMyomegalinGenetics and epigenetic pathways of disease Functional Neurogenomics [NCMLS 6]CattleAnkyrin repeatCiliary baseIntracellular transport030217 neurology & neurosurgerySensorineuronal degeneration
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A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the hair bundle in its cohesion, orientation and differential growth

2008

The planar polarity and staircase-like pattern of the hair bundle are essential to the mechanoelectrical transduction function of inner ear sensory cells. Mutations in genes encoding myosin VIIa, harmonin, cadherin 23,protocadherin 15 or sans cause Usher syndrome type I (USH1, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa leading to blindness) in humans and hair bundle disorganization in mice. Whether the USH1 proteins are involved in common hair bundle morphogenetic processes is unknown. Here, we show that mouse models for the five USH1 genetic forms share hair bundle morphological defects. Hair bundle fragmentation and misorientation (25-52° mean ki…

Stereocilia (inner ear)Cadherin Related ProteinsProtocadherinCell Cycle ProteinsNerve Tissue ProteinsMyosinsBiologyMechanotransduction CellularMiceCDH23Pregnancyotorhinolaryngologic diseasesmedicineAnimalsHumansInner earProtein PrecursorsMolecular BiologyActinMice KnockoutCadherinDyneinsAnatomyCadherinsMice Mutant StrainsCochleaCell biologyCytoskeletal ProteinsDisease Models AnimalPhenotypemedicine.anatomical_structureMyosin VIIaMicroscopy Electron ScanningFemalesense organsCarrier ProteinsUsher SyndromesTip linkPCDH15Developmental BiologyDevelopment
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