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Pesquisa : D05.750.078.593.765 [Categoria DeCS]
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[PMID]:27773721
[Au] Autor:Tajerian M; Hung V; Khan H; Lahey LJ; Sun Y; Birklein F; Krämer HH; Robinson WH; Kingery WS; Clark JD
[Ad] Endereço:Veterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA. Electronic address: maral@stanford.edu.
[Ti] Título:Identification of KRT16 as a target of an autoantibody response in complex regional pain syndrome.
[So] Source:Exp Neurol;287(Pt 1):14-20, 2017 Jan.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Using a mouse model of complex regional pain syndrome (CRPS), our goal was to identify autoantigens in the skin of the affected limb. METHODS: A CRPS-like state was induced using the tibia fracture/cast immobilization model. Three weeks after fracture, hindpaw skin was homogenized, run on 2-d gels, and probed by sera from fracture and control mice. Spots of interest were analyzed by liquid chromatography-mass spectroscopy (LC-MS) and the list of targets validated by examining their abundance and subcellular localization. In order to measure the autoantigenicity of selected protein targets, we quantified the binding of IgM in control and fracture mice sera, as well as in control and CRPS human sera, to the recombinant protein. RESULTS: We show unique binding between fracture skin extracts and fracture sera, suggesting the presence of auto-antigens. LC-MS analysis provided us a list of potential targets, some of which were upregulated after fracture (KRT16, eEF1a1, and PRPH), while others showed subcellular-redistribution and increased membrane localization (ANXA2 and ENO3). No changes in protein citrullination or carbamylation were observed. In addition to increased abundance, KRT16 demonstrated autoantigenicity, since sera from both fracture mice and CRPS patients showed increased autoantibody binding to recombinant kRT16 protein. CONCLUSIONS: Pursuing autoimmune contributions to CRPS provides a novel approach to understanding the condition and may allow the development of mechanism-based therapies. The identification of autoantibodies against KRT16 as a biomarker in mice and in humans is a critical step towards these goals, and towards redefining CRPS as having an autoimmune etiology.
[Mh] Termos MeSH primário: Autoantígenos/metabolismo
Síndromes da Dor Regional Complexa/sangue
Síndromes da Dor Regional Complexa/patologia
Queratina-6/imunologia
Queratina-6/metabolismo
Pele/metabolismo
Pele/ultraestrutura
Regulação para Cima/fisiologia
[Mh] Termos MeSH secundário: Adulto
Animais
Anexina A2/metabolismo
Autoantígenos/genética
Modelos Animais de Doenças
Membro Posterior/inervação
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Meia-Idade
Fator 1 de Elongação de Peptídeos/metabolismo
Periferinas/metabolismo
Fosfopiruvato Hidratase/metabolismo
Frações Subcelulares/metabolismo
Fraturas da Tíbia/sangue
Fraturas da Tíbia/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ANXA2 protein, human); 0 (Annexin A2); 0 (Autoantigens); 0 (EEF1A1 protein, human); 0 (KRT6A protein, human); 0 (Keratin-6); 0 (PRPH protein, human); 0 (Peptide Elongation Factor 1); 0 (Peripherins); EC 4.2.1.11 (Phosphopyruvate Hydratase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161028
[St] Status:MEDLINE


  2 / 660 MEDLINE  
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[PMID]:28723922
[Au] Autor:Sahaboglu A; Sharif A; Feng L; Secer E; Zrenner E; Paquet-Durand F
[Ad] Endereço:Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.
[Ti] Título:Temporal progression of PARP activity in the Prph2 mutant rd2 mouse: Neuroprotective effects of the PARP inhibitor PJ34.
[So] Source:PLoS One;12(7):e0181374, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripherin (peripherin/rds) is a membrane-associated protein that plays a critical role in the morphogenesis of rod and cone photoreceptor outer segments. Mutations in the corresponding PRPH2 gene cause different types of retinal dystrophies characterized by a loss of photoreceptors. Over activation of poly-ADP-ribose polymerase (PARP) was previously shown to be involved in different animal models for hereditary retinal dystrophies. This includes the rd2 mouse, which suffers from a human homologous mutation in the PRPH2 gene. In the present study, we show that increased retinal PARP activity and poly-ADP-ribosylation of proteins occurs before the peak of rd2 photoreceptor degeneration. Inhibition of PARP activity with the well-characterized PARP inhibitor PJ34 decreased the levels of poly-ADP-ribosylation and photoreceptor cell death. These results suggest a causal involvement of PARP in photoreceptor degeneration caused by peripherin mutations and highlight the possibility to use PARP inhibition for the mutation-independent treatment of hereditary retinal dystrophies.
[Mh] Termos MeSH primário: Fármacos Neuroprotetores/farmacologia
Periferinas/metabolismo
Fenantrenos/farmacologia
Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores
Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos
Degeneração Retiniana/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Knockout
Periferinas/genética
Poli(ADP-Ribose) Polimerase-1/metabolismo
Células Fotorreceptoras Retinianas Cones/metabolismo
Degeneração Retiniana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride); 0 (Neuroprotective Agents); 0 (Peripherins); 0 (Phenanthrenes); 0 (Poly(ADP-ribose) Polymerase Inhibitors); 0 (Rds protein, mouse); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181374


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[PMID]:28404842
[Au] Autor:Thellman NM; Botting C; Madaj Z; Triezenberg SJ
[Ad] Endereço:Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, USA.
[Ti] Título:An Immortalized Human Dorsal Root Ganglion Cell Line Provides a Novel Context To Study Herpes Simplex Virus 1 Latency and Reactivation.
[So] Source:J Virol;91(12), 2017 Jun 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v- oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin. Infection of mature HD10.6 neurons by herpes simplex virus 1 (HSV-1) results in a delayed but productive infection. However, infection at a low multiplicity of infection (MOI) in the presence of acyclovir results in a quiescent infection resembling latency in which viral genomes are retained in a low number of neurons, viral gene expression is minimal, and infectious virus is not released. At least some of the quiescent viral genomes retain the capacity to reactivate, resulting in viral DNA replication and release of infectious virus. Reactivation can be induced by depletion of nerve growth factor; other commonly used reactivation stimuli have no significant effect. Infections by herpes simplex viruses (HSV) cause painful cold sores or genital lesions in many people; less often, they affect the eye or even the brain. After the initial infection, the virus remains inactive or latent in nerve cells that sense the region where that infection occurred. To learn how virus maintains and reactivates from latency, studies are done in neurons taken from rodents or in whole animals to preserve the full context of infection. However, some cellular mechanisms involved in HSV infection in rodents are different from those in humans. We describe the use of a human cell line that has the properties of a sensory neuron. HSV infection in these cultured cells shows the properties expected for a latent infection, including reactivation to produce newly infectious virus. Thus, we now have a cell culture model for latency that is derived from the normal host for this virus.
[Mh] Termos MeSH primário: Gânglios Espinais/virologia
Herpesvirus Humano 1/fisiologia
Células Receptoras Sensoriais/virologia
Ativação Viral
Latência Viral
[Mh] Termos MeSH secundário: Aciclovir/farmacologia
Antivirais/farmacologia
Técnicas de Cultura de Células
Linhagem Celular
Doxiciclina/farmacologia
Gânglios Espinais/efeitos dos fármacos
Regulação Viral da Expressão Gênica
Herpes Simples/virologia
Seres Humanos
Glicoproteínas de Membrana/genética
Fator de Crescimento Neural/farmacologia
Periferinas/genética
Proteínas Tirosina Quinases/genética
Proteínas Proto-Oncogênicas c-ret/genética
Receptor trkA/genética
Receptor trkB
Receptor trkC/genética
Células Receptoras Sensoriais/fisiologia
Liberação de Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Membrane Glycoproteins); 0 (PRPH protein, human); 0 (Peripherins); 0 (TRKA protein, human); 9061-61-4 (Nerve Growth Factor); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Proto-Oncogene Proteins c-ret); EC 2.7.10.1 (RET protein, human); EC 2.7.10.1 (Receptor, trkA); EC 2.7.10.1 (Receptor, trkB); EC 2.7.10.1 (Receptor, trkC); EC 2.7.10.1 (tropomyosin-related kinase-B, human); N12000U13O (Doxycycline); X4HES1O11F (Acyclovir)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE


  4 / 660 MEDLINE  
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[PMID]:28400442
[Au] Autor:Molday RS; Goldberg AFX
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada molday@mail.ubc.ca goldberg@oakland.edu.
[Ti] Título:Peripherin diverts ciliary ectosome release to photoreceptor disc morphogenesis.
[So] Source:J Cell Biol;216(5):1227-1229, 2017 May 01.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Formation of membrane discs in photoreceptor cells requires evagination of its ciliary plasma membrane by an unknown molecular mechanism. Salinas et al. (2017. https://doi.org/10.1083/jcb.201608081) show that peripherin (also known as peripherin-2 or peripherin-2/rds) diverts membrane traffic to photoreceptor disc formation by inhibiting ectosome release from the cilium.
[Mh] Termos MeSH primário: Micropartículas Derivadas de Células
Periferinas
[Mh] Termos MeSH secundário: Proteínas do Citoesqueleto
Proteínas de Filamentos Intermediários
Glicoproteínas de Membrana
Morfogênese
Proteínas do Tecido Nervoso
Células Fotorreceptoras
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytoskeletal Proteins); 0 (Intermediate Filament Proteins); 0 (Membrane Glycoproteins); 0 (Nerve Tissue Proteins); 0 (Peripherins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201703020


  5 / 660 MEDLINE  
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[PMID]:28381413
[Au] Autor:Salinas RY; Pearring JN; Ding JD; Spencer WJ; Hao Y; Arshavsky VY
[Ad] Endereço:Department of Ophthalmology, Duke University, Durham, NC 27710.
[Ti] Título:Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release.
[So] Source:J Cell Biol;216(5):1489-1499, 2017 May 01.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The primary cilium is a highly conserved organelle housing specialized molecules responsible for receiving and processing extracellular signals. A recently discovered property shared across many cilia is the ability to release small vesicles called ectosomes, which are used for exchanging protein and genetic material among cells. In this study, we report a novel role for ciliary ectosomes in building the elaborate photoreceptor outer segment filled with hundreds of tightly packed "disc" membranes. We demonstrate that the photoreceptor cilium has an innate ability to release massive amounts of ectosomes. However, this process is suppressed by the disc-specific protein peripherin, which enables retained ectosomes to be morphed into discs. This new function of peripherin is performed independently from its well-established role in maintaining the high curvature of disc edges, and each function is fulfilled by a separate part of peripherin's molecule. Our findings explain how the outer segment structure evolved from the primary cilium to provide photoreceptor cells with vast membrane surfaces for efficient light capture.
[Mh] Termos MeSH primário: Micropartículas Derivadas de Células/metabolismo
Cílios/metabolismo
Periferinas/metabolismo
Células Fotorreceptoras/metabolismo
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peripherins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201608081


  6 / 660 MEDLINE  
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[PMID]:28325841
[Au] Autor:Milstein ML; Kimler VA; Ghatak C; Ladokhin AS; Goldberg AFX
[Ad] Endereço:From the Eye Research Institute, Oakland University, Rochester, Michigan 48309 and.
[Ti] Título:An inducible amphipathic helix within the intrinsically disordered C terminus can participate in membrane curvature generation by peripherin-2/rds.
[So] Source:J Biol Chem;292(19):7850-7865, 2017 May 12.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripherin-2/rds is required for biogenesis of vertebrate photoreceptor outer segment organelles. Its localization at the high-curvature rim domains of outer segment disk membranes suggests that it may act to shape these structures; however, the molecular function of this protein is not yet resolved. Here, we apply biochemical, biophysical, and imaging techniques to elucidate the role(s) played by the protein's intrinsically disordered C-terminal domain and an incipient amphipathic α-helix contained within it. We investigated a deletion mutant lacking only this α-helix in stable cell lines and photoreceptors. We also studied a soluble form of the full-length ∼7-kDa cytoplasmic C terminus in cultured cells and purified from The α-helical motif was not required for protein biosynthesis, tetrameric subunit assembly, tetramer polymerization, localization at disk rims, interaction with GARP2, or the generation of membrane curvature. Interestingly, however, loss of the helical motif up-regulated membrane curvature generation , introducing the possibility that it may regulate this activity in photoreceptors. Furthermore, the incipient α-helix (within the purified soluble C terminus) partitioned into membranes only when its acidic residues were neutralized by protonation. This suggests that within the context of full-length peripherin-2/rds, partitioning would most likely occur at a bilayer interfacial region, potentially adjacent to the protein's transmembrane domains. In sum, this study significantly strengthens the evidence that peripherin-2/rds functions directly to shape the high-curvature rim domains of the outer segment disk and suggests that the protein's C terminus may modulate membrane curvature-generating activity present in other protein domains.
[Mh] Termos MeSH primário: Membrana Celular/química
Proteínas Intrinsicamente Desordenadas/química
Periferinas/química
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Células COS
Bovinos
Cercopithecus aethiops
Dicroísmo Circular
Canais de Cátion Regulados por Nucleotídeos Cíclicos/química
Citoplasma/metabolismo
Escherichia coli/metabolismo
Células HEK293
Seres Humanos
Mutação
Periferinas/fisiologia
Fosfolipídeos/química
Domínios Proteicos
Dobramento de Proteína
Multimerização Proteica
Estrutura Secundária de Proteína
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclic Nucleotide-Gated Cation Channels); 0 (Intrinsically Disordered Proteins); 0 (Peripherins); 0 (Phospholipids); 0 (glutamic acid-rich protein-2, human)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768143


  7 / 660 MEDLINE  
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[PMID]:28118374
[Au] Autor:Nishimura K; Noda T; Dabdoub A
[Ad] Endereço:Shiga Medical Center Research Institute, Moriyama, Shiga, Japan.
[Ti] Título:Dynamic Expression of Sox2, Gata3, and Prox1 during Primary Auditory Neuron Development in the Mammalian Cochlea.
[So] Source:PLoS One;12(1):e0170568, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Primary auditory neurons (PANs) connect cochlear sensory hair cells in the mammalian inner ear to cochlear nucleus neurons in the brainstem. PANs develop from neuroblasts delaminated from the proneurosensory domain of the otocyst and keep maturing until the onset of hearing after birth. There are two types of PANs: type I, which innervate the inner hair cells (IHCs), and type II, which innervate the outer hair cells (OHCs). Glial cells surrounding these neurons originate from neural crest cells and migrate to the spiral ganglion. Several transcription factors are known to regulate the development and differentiation of PANs. Here we systematically examined the spatiotemporal expression of five transcription factors: Sox2, Sox10, Gata3, Mafb, and Prox1 from early delamination at embryonic day (E) 10.5 to adult. We found that Sox2 and Sox10 were initially expressed in the proneurosensory cells in the otocyst (E10.5). By E12.75 both Sox2 and Sox10 were downregulated in the developing PANs; however, Sox2 expression transiently increased in the neurons around birth. Furthermore, both Sox2 and Sox10 continued to be expressed in spiral ganglion glial cells. We also show that Gata3 and Prox1 were first expressed in all developing neurons, followed by a decrease in expression of Gata3 and Mafb in type I PANs and Prox1 in type II PANs as they matured. Moreover, we describe two subtypes of type II neurons based on Peripherin expression. These results suggest that Sox2, Gata3 and Prox1 play a role during neurogenesis as well as maturation of the PANs.
[Mh] Termos MeSH primário: Cóclea/embriologia
Fator de Transcrição GATA3/biossíntese
Regulação da Expressão Gênica no Desenvolvimento
Proteínas de Homeodomínio/biossíntese
Proteínas do Tecido Nervoso/biossíntese
Neurogênese
Fatores de Transcrição SOXB1/biossíntese
Células Receptoras Sensoriais/metabolismo
Gânglio Espiral da Cóclea/embriologia
Proteínas Supressoras de Tumor/biossíntese
[Mh] Termos MeSH secundário: Animais
Núcleo Celular/metabolismo
Cóclea/crescimento & desenvolvimento
Cóclea/metabolismo
Fator de Transcrição GATA3/genética
Técnicas de Introdução de Genes
Genes Reporter
Idade Gestacional
Proteínas de Homeodomínio/genética
Fator de Transcrição MafB/biossíntese
Fator de Transcrição MafB/genética
Camundongos
Proteínas do Tecido Nervoso/genética
Crista Neural/metabolismo
Células-Tronco Neurais/metabolismo
Neurogênese/genética
Neuroglia/metabolismo
Periferinas/biossíntese
Periferinas/genética
Proteínas Recombinantes de Fusão/biossíntese
Fatores de Transcrição SOXB1/genética
Fatores de Transcrição SOXE/biossíntese
Fatores de Transcrição SOXE/genética
Células Receptoras Sensoriais/classificação
Gânglio Espiral da Cóclea/metabolismo
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GATA3 Transcription Factor); 0 (Gata3 protein, mouse); 0 (Homeodomain Proteins); 0 (MafB Transcription Factor); 0 (Mafb protein, mouse); 0 (Nerve Tissue Proteins); 0 (Peripherins); 0 (Prph1 protein, mouse); 0 (Recombinant Fusion Proteins); 0 (SOXB1 Transcription Factors); 0 (SOXE Transcription Factors); 0 (Sox10 protein, mouse); 0 (Sox2 protein, mouse); 0 (Tumor Suppressor Proteins); 0 (prospero-related homeobox 1 protein)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170125
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170568


  8 / 660 MEDLINE  
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[PMID]:28053051
[Au] Autor:Conley SM; Stuck MW; Watson JN; Naash MI
[Ad] Endereço:Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
[Ti] Título:Rom1 converts Y141C-Prph2-associated pattern dystrophy to retinitis pigmentosa.
[So] Source:Hum Mol Genet;26(3):509-518, 2017 Feb 01.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mutations in peripherin 2 (PRPH2), also known as retinal degeneration slow/RDS, lead to various retinal degenerations including retinitis pigmentosa (RP) and macular/pattern dystrophy (MD/PD). PRPH2-associated disease is often characterized by a phenotypic variability even within families carrying the same mutation, raising interest in potential modifiers. PRPH2 oligomerizes with its homologue rod outer segment (OS) membrane protein 1 (ROM1), and non-pathogenic PRPH2/ROM1 mutations, when present together, lead to digenic RP. We asked whether ROM1 could modify the phenotype of a PRPH2 mutation associated with a high degree of intrafamilial phenotypic heterogeneity: Y141C. In vitro, Y141C-Prph2 showed signs of retention in the endoplasmic reticulum (ER), however co-expression with Rom1 rescued this phenotype. In the heterozygous Y141C knockin mouse model (Prph2Y/+), Y141C-Prph2 and Rom1 formed abnormal complexes but were present at normal levels. Abnormal complexes were eliminated in the absence of Rom1 (Prph2Y/+/Rom1-/-) and total Prph2 levels were reduced to those found in the haploinsufficient Prph2+/- RP model. The biochemical changes had functional and structural consequences; while Prph2Y/+ animals exhibited a cone-rod electroretinogram defect, Prph2Y/+/Rom1-/- animals displayed a rod-dominant phenotype and OSs similar to those seen in the Prph2+/-. These data show that ablation of Rom1 results in the conversion of an MD/PD phenotype characterized by cone functional defects and the formation of abnormal Prph2/Rom1 complexes to an RP phenotype characterized by rod-dominant functional defects and reductions in total Prph2 protein. Thus one method by which ROM1 may act as a disease modifier is by contributing to the large variability in PRPH2-associated disease phenotypes.
[Mh] Termos MeSH primário: Periferinas/genética
Degeneração Retiniana/genética
Retinite Pigmentosa/genética
Tetraspaninas/genética
[Mh] Termos MeSH secundário: Animais
Retículo Endoplasmático/genética
Retículo Endoplasmático/patologia
Regulação da Expressão Gênica
Técnicas de Introdução de Genes
Seres Humanos
Degeneração Macular/genética
Degeneração Macular/patologia
Camundongos
Complexos Multiproteicos/biossíntese
Complexos Multiproteicos/química
Complexos Multiproteicos/genética
Mutação
Linhagem
Periferinas/biossíntese
Periferinas/química
Fenótipo
Células Fotorreceptoras de Vertebrados/química
Células Fotorreceptoras de Vertebrados/metabolismo
Multimerização Proteica
Degeneração Retiniana/patologia
Retinite Pigmentosa/patologia
Tetraspaninas/biossíntese
Tetraspaninas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Multiprotein Complexes); 0 (Peripherins); 0 (RDS protein, human); 0 (ROM1 protein, human); 0 (Tetraspanins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddw408


  9 / 660 MEDLINE  
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[PMID]:28005406
[Au] Autor:Ramkumar HL; Gudiseva HV; Kishaba KT; Suk JJ; Verma R; Tadimeti K; Thorson JA; Ayyagari R
[Ad] Endereço:1 Shiley Eye Institute, Jacobs Retina Center, University of California , San Diego, La Jolla, California.
[Ti] Título:A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.
[So] Source:Genet Test Mol Biomarkers;21(2):66-73, 2017 Feb.
[Is] ISSN:1945-0257
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIM: To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). METHODS: After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). RESULTS: Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). CONCLUSIONS: Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.
[Mh] Termos MeSH primário: Distrofias Retinianas/diagnóstico
Distrofias Retinianas/genética
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Bestrofinas
Canais de Cloreto/genética
Canais de Cloreto/metabolismo
Análise Mutacional de DNA/métodos
Éxons
Proteínas do Olho/genética
Proteínas do Olho/metabolismo
Feminino
Estudos de Associação Genética
Aconselhamento Genético
Testes Genéticos/métodos
Heterozigoto
Seres Humanos
Masculino
Técnicas de Diagnóstico Molecular/métodos
Mutação
Periferinas/genética
Periferinas/metabolismo
Retinite Pigmentosa/genética
Inibidor Tecidual de Metaloproteinase-3/genética
Inibidor Tecidual de Metaloproteinase-3/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCA4 protein, human); 0 (BEST1 protein, human); 0 (Bestrophins); 0 (Chloride Channels); 0 (Eye Proteins); 0 (Peripherins); 0 (RDS protein, human); 0 (TIMP3 protein, human); 0 (Tissue Inhibitor of Metalloproteinase-3)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE
[do] DOI:10.1089/gtmb.2016.0251


  10 / 660 MEDLINE  
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[PMID]:27696081
[Au] Autor:Vyas P; Wu JS; Zimmerman A; Fuchs P; Glowatzki E
[Ad] Endereço:The Center for Hearing and Balance, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 824, Baltimore, MD, 21205, USA.
[Ti] Título:Tyrosine Hydroxylase Expression in Type II Cochlear Afferents in Mice.
[So] Source:J Assoc Res Otolaryngol;18(1):139-151, 2017 Feb.
[Is] ISSN:1438-7573
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acoustic information propagates from the ear to the brain via spiral ganglion neurons that innervate hair cells in the cochlea. These afferents include unmyelinated type II fibers that constitute 5 % of the total, the majority being myelinated type I neurons. Lack of specific genetic markers of type II afferents in the cochlea has been a roadblock in studying their functional role. Unexpectedly, type II afferents were visualized by reporter proteins induced by tyrosine hydroxylase (TH)-driven Cre recombinase. The present study was designed to determine whether TH-driven Cre recombinase (TH-2A-CreER) provides a selective and reliable tool for identification and genetic manipulation of type II rather than type I cochlear afferents. The "TH-2A-CreER neurons" radiated from the spiral lamina, crossed the tunnel of Corti, turned towards the base of the cochlea, and traveled beneath the rows of outer hair cells. Neither the processes nor the somata of TH-2A-CreER neurons were labeled by antibodies that specifically labeled type I afferents and medial efferents. TH-2A-CreER-positive processes partially co-labeled with antibodies to peripherin, a known marker of type II afferents. Individual TH-2A-CreER neurons gave off short branches contacting 7-25 outer hair cells (OHCs). Only a fraction of TH-2A-CreER boutons were associated with CtBP2-immunopositive ribbons. These results show that TH-2A-CreER provides a selective marker for type II versus type I afferents and can be used to describe the morphology and arborization pattern of type II cochlear afferents in the mouse cochlea.
[Mh] Termos MeSH primário: Cóclea/inervação
Neurônios Aferentes/enzimologia
Tirosina 3-Mono-Oxigenase/análise
[Mh] Termos MeSH secundário: Animais
Feminino
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Endogâmicos CBA
Neurônios Aferentes/efeitos dos fármacos
Neurônios Aferentes/ultraestrutura
Periferinas/análise
Tamoxifeno/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peripherins); 094ZI81Y45 (Tamoxifen); EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE
[do] DOI:10.1007/s10162-016-0591-7



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