Search results for "scaffold"

showing 10 items of 470 documents

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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The Tegument Protein pp65 of Human Cytomegalovirus Acts as an Optional Scaffold Protein That Optimizes Protein Uploading into Viral Particles

2014

ABSTRACT The mechanisms that lead to the tegumentation of herpesviral particles are only poorly defined. The phosphoprotein 65 (pp65) is the most abundant constituent of the virion tegument of human cytomegalovirus (HCMV). It is, however, nonessential for virion formation. This seeming discrepancy has not met with a satisfactory explanation regarding the role of pp65 in HCMV particle morphogenesis. Here, we addressed the question of how the overall tegument composition of the HCMV virion depended on pp65 and how the lack of pp65 influenced the packaging of particular tegument proteins. To investigate this, we analyzed the proteomes of pp65-positive (pp65pos) and pp65-negative (pp65neg) viri…

Scaffold proteinHuman cytomegalovirusProteomevirusesImmunologyMorphogenesisCytomegalovirusBiologyMicrobiologyMass SpectrometryViral Matrix ProteinsVirologymedicineHumansGeneViral matrix proteinVirus AssemblyStructure and AssemblyVirionvirus diseasesViral tegumentbiochemical phenomena metabolism and nutritionPhosphoproteinsmedicine.diseaseVirologyCell biologysurgical procedures operativeInsect SciencePhosphoproteinProteomeGene DeletionJournal of Virology
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Direct binding of Magi2 to the USH1G protein SANS links the periciliary USH protein network to endocytosis

2012

The human Usher syndrome (USH) is the most common form of combined deaf-blindness. The encoded molecules are integrated into protein networks by scaffolds including the USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain). Previous studies indicated SANS´ participation in vesicle transport and cargo handover at the periciliary region of photoreceptor cells. To decipher the precise cellular role of SANS, we searched for interacting partners. Therefore we adopted a yeast-2-hybrid screen of a retinal cDNA library using SANS´ C-terminus as bait. Amongst others we identified the MAGUK protein Magi2 (membrane-associated guanylate kinase inverted-2) as putative binding p…

Scaffold proteinImmunoelectron microscopyCell BiologyBiologyEndocytosisInteractomePhotoreceptor cellCell biologyVesicular transport proteinmedicine.anatomical_structureCiliary pocketPoster PresentationmedicineAnkyrin repeatCilia
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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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The GRIP1/14-3-3 Pathway Coordinates Cargo Trafficking and Dendrite Development

2014

SummaryRegulation of cargo transport via adaptor molecules is essential for neuronal development. However, the role of PDZ scaffolding proteins as adaptors in neuronal cargo trafficking is still poorly understood. Here, we show by genetic deletion in mice that the multi-PDZ domain scaffolding protein glutamate receptor interacting protein 1 (GRIP1) is required for dendrite development. We identify an interaction between GRIP1 and 14-3-3 proteins that is essential for the function of GRIP1 as an adaptor protein in dendritic cargo transport. Mechanistically, 14-3-3 binds to the kinesin-1 binding region in GRIP1 in a phospho-dependent manner and detaches GRIP1 from the kinesin-1 motor protein …

Scaffold proteinPDZ domainKinesinsNerve Tissue ProteinsDendriteBiologyGeneral Biochemistry Genetics and Molecular BiologyMotor proteinGene Knockout TechniquesMiceMicrotubulemedicineAnimalsMolecular BiologyAdaptor Proteins Signal TransducingPoint mutationSignal transducing adaptor proteinDendritesCell BiologyCell biologyProtein Transportmedicine.anatomical_structure14-3-3 ProteinsMutationCarrier ProteinsFunction (biology)Protein BindingSignal TransductionTranscription FactorsDevelopmental BiologyDevelopmental Cell
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The Usher syndrome 1G protein SANS participates in the transport of ciliary cargo in photoreceptor cells

2012

Human Usher syndrome (USH) is the most common form of combined deaf-blindness, characterized by profound congenital deafness, constant vestibular dysfunction and pre-pubertal onset of retinitis pigmentosa. The USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain) is associated with microtubules and mediates a transport related periciliary protein network in photoreceptor cells. Here we aim to enlighten the involvement of SANS in ciliary transport of photoreceptor cells by identifying proteins associated with SANS in transport complexes. In Y2H screen of retinal cDNA library we identified the direct binding of SANS to dynactin-1 (p150Glued), a subunit of the dynacti…

Scaffold proteinRetinal degenerationGeneticsOpsinlcsh:CytologyProtein subunitCiliumCell BiologyBiologymedicine.diseaseOpsin transportCell biologyMicrotubuleRetinitis pigmentosaPoster Presentationmedicinesense organslcsh:QH573-671Cilia
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