Base de dados : MEDLINE
Pesquisa : D08.811.277.040.330.200.300 [Categoria DeCS]
Referências encontradas : 49 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 5 ir para página              

  1 / 49 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27692902
[Au] Autor:Trinh J; Gustavsson EK; Vilariño-Güell C; Bortnick S; Latourelle J; McKenzie MB; Tu CS; Nosova E; Khinda J; Milnerwood A; Lesage S; Brice A; Tazir M; Aasly JO; Parkkinen L; Haytural H; Foroud T; Myers RH; Sassi SB; Hentati E; Nabli F; Farhat E; Amouri R; Hentati F; Farrer MJ
[Ad] Endereço:Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
[Ti] Título:DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study.
[So] Source:Lancet Neurol;15(12):1248-1256, 2016 Nov.
[Is] ISSN:1474-4465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance. METHODS: Between 2006 and 2012, we recruited Arab-Berber patients with Parkinson's disease and their family members (aged 18 years or older) at the Mongi Ben Hamida National Institute of Neurology (Tunis, Tunisia). Patients with Parkinson's disease were diagnosed by movement disorder specialists in accordance with the UK Parkinson's Disease Society Brain Bank criteria, without exclusion of familial parkinsonism. LRRK2 carrier status was confirmed by Sanger sequencing or TaqMan SNP assays-on-demand. We did genome-wide linkage analysis using data from multi-incident Arab-Berber families with Parkinson's disease and LRRK2 Gly2019Ser (with both affected and unaffected family members). We assessed Parkinson's disease age of onset both as a categorical variable (dichotomised by median onset) and as a quantitative trait. We used data from another cohort of unrelated Tunisian LRRK2 Gly2019Ser carriers for subsequent locus-specific genotyping and association analyses. Whole-genome sequencing in a subset of 14 unrelated Arab-Berber individuals who were LRRK2 Gly2019Ser carriers (seven with early-onset disease and seven elderly unaffected individuals) subsequently informed imputation and haplotype analyses. We replicated the findings in separate series of LRRK2 Gly2019Ser carriers originating from Algeria, France, Norway, and North America. We also investigated associations between genotype, gene, and protein expression in human striatal tissues and murine LRRK2 Gly2019Ser cortical neurons. FINDINGS: Using data from 41 multi-incident Arab-Berber families with Parkinson's disease and LRRK2 Gly2019Ser (150 patients and 103 unaffected family members), we identified significant linkage on chromosome 1q23.3 to 1q24.3 (non-parametric logarithm of odds score 2·9, model-based logarithm of odds score 4·99, θ=0 at D1S2768). In a cohort of unrelated Arab-Berber LRRK2 Gly2019Ser carriers, subsequent association mapping within the linkage region suggested genetic variability within DNM3 as an age-of-onset modifier of disease (n=232; rs2421947; haplotype p=1·07 × 10 ). We found that DNM3 rs2421947 was a haplotype tag for which the median onset of LRRK2 parkinsonism in GG carriers was 12·5 years younger than that of CC carriers (Arab-Berber cohort, hazard ratio [HR] 1·89, 95% CI 1·20-2·98). Replication analyses in separate series from Algeria, France, Norway, and North America (n=263) supported this finding (meta-analysis HR 1·61, 95% CI 1·15-2·27, p=0·02). In human striatum, DNM3 expression varied as a function of rs2421947 genotype, and dynamin-3 localisation was perturbed in murine LRRK2 Gly2019Ser cortical neurons. INTERPRETATION: Genetic variability in DNM3 modifies age of onset for LRRK2 Gly2019Ser parkinsonism and informs disease-relevant translational neuroscience. Our results could be useful in genetic counselling for carriers of this mutation and in clinical trial design. FUNDING: The Canada Excellence Research Chairs (CERC), Leading Edge Endowment Fund (LEEF), Don Rix BC Leadership Chair in Genetic Medicine, National Institute on Aging, National Institute of Neurological Disorders and Stroke, the Michael J Fox Foundation, Mayo Foundation, the Roger de Spoelberch Foundation, and GlaxoSmithKline.
[Mh] Termos MeSH primário: Dinamina III/genética
Ligação Genética/genética
Estudo de Associação Genômica Ampla
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética
Doença de Parkinson/genética
[Mh] Termos MeSH secundário: Adulto
Idade de Início
Idoso
Idoso de 80 Anos ou mais
Árabes/genética
Feminino
Seres Humanos
Masculino
Meia-Idade
Doença de Parkinson/etnologia
Linhagem
Penetrância
Tunísia/etnologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (LRRK2 protein, human); EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161004
[St] Status:MEDLINE


  2 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27508440
[Au] Autor:Li J; Barylko B; Eichorst JP; Mueller JD; Albanesi JP; Chen Y
[Ad] Endereço:Department of Physics, University of Minnesota, Minneapolis, Minnesota.
[Ti] Título:Association of Endophilin B1 with Cytoplasmic Vesicles.
[So] Source:Biophys J;111(3):565-576, 2016 Aug 09.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endophilins are SH3- and BAR domain-containing proteins implicated in membrane remodeling and vesicle formation. Endophilins A1 and A2 promote the budding of endocytic vesicles from the plasma membrane, whereas endophilin B1 has been implicated in vesicle budding from intracellular organelles, including the trans-Golgi network and late endosomes. We previously reported that endophilins A1 and A2 exist almost exclusively as soluble dimers in the cytosol. Here, we present results of fluorescence fluctuation spectroscopy analyses indicating that, in contrast, the majority of endophilin B1 is present in multiple copies on small, highly mobile cytoplasmic vesicles. Formation of these vesicles was enhanced by overexpression of wild-type dynamin 2, but suppressed by expression of a catalytically inactive dynamin 2 mutant. Using dual-color heterospecies partition analysis, we identified the epidermal growth factor receptor on endophilin B1 vesicles. Moreover, a proportion of endophilin B1 vesicles also contained caveolin, whereas clathrin was almost undetectable on those vesicles. These results raise the possibility that endophilin B1 participates in dynamin 2-dependent formation of a population of transport vesicles distinct from those generated by A-type endophilins.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Vesículas Citoplasmáticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Caveolinas/metabolismo
Linhagem Celular
Dinamina III/metabolismo
Seres Humanos
Ligantes
Ligação Proteica
Transporte Proteico
Ratos
Receptor do Fator de Crescimento Epidérmico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Caveolins); 0 (Ligands); 0 (SH3GLB1 protein, human); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160811
[St] Status:MEDLINE


  3 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27251629
[Au] Autor:Fan F; Funk L; Lou X
[Ad] Endereço:Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53706.
[Ti] Título:Dynamin 1- and 3-Mediated Endocytosis Is Essential for the Development of a Large Central Synapse In Vivo.
[So] Source:J Neurosci;36(22):6097-115, 2016 Jun 01.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Dynamin is a large GTPase crucial for endocytosis and sustained neurotransmission, but its role in synapse development in the mammalian brain has received little attention. We addressed this question using the calyx of Held (CH), a large nerve terminal in the auditory brainstem in mice. Tissue-specific ablation of different dynamin isoforms bypasses the early lethality of conventional knock-outs and allows us to examine CH development in a native brain circuit. Individual gene deletion of dynamin 1, a primary dynamin isoform in neurons, as well as dynamin 2 and 3, did not affect CH development. However, combined tissue-specific knock-out of both dynamin 1 and 3 (cDKO) severely impaired CH formation and growth during the first postnatal week, and the phenotypes were exacerbated by further additive conditional knock-out of dynamin 2. The developmental defect of CH in cDKO first became evident on postnatal day 3 (P3), a time point when CH forms and grows abruptly. This is followed by a progressive loss of postsynaptic neurons and increased glial infiltration late in development. However, early CH synaptogenesis before protocalyx formation was not altered in cDKO. Functional maturation of synaptic transmission in the medial nucleus of the trapezoid body in cDKO was impeded during development and accompanied by an increase in the membrane excitability of medial nucleus of the trapezoid body neurons. This study provides compelling genetic evidence that CH formation requires dynamin 1- and 3-mediated endocytosis in vivo, indicating a critical role of dynamin in synaptic development, maturation, and subsequent maintenance in the mammalian brain. SIGNIFICANCE STATEMENT: Synaptic development has been increasingly implicated in numerous brain disorders. Dynamin plays a crucial role in clathrin-mediated endocytosis and synaptic transmission at nerve terminals, but its potential role in synaptic development in the native brain circuitry is unclear. Using the calyx of Held, a giant nerve terminal in the mouse brainstem, we evaluated the role of dynamin in this process by using tissue-specific knock-out (KO) of three different dynamin isoforms (dynamin 1, 2, and 3) individually and in combination. Our data demonstrated that dynamin is required for the formation, functional maturation, and subsequent survival of the calyx of Held. This study highlights the important role of dynamin-mediated endocytosis in the development of central synapses in the mammalian brain.
[Mh] Termos MeSH primário: Tronco Encefálico/citologia
Tronco Encefálico/crescimento & desenvolvimento
Dinamina III/deficiência
Dinamina I/deficiência
Endocitose/fisiologia
Sinapses/fisiologia
[Mh] Termos MeSH secundário: Fatores Etários
Animais
Animais Recém-Nascidos
Dinamina I/genética
Dinamina III/genética
Proteína 2 de Resposta de Crescimento Precoce/genética
Proteína 2 de Resposta de Crescimento Precoce/metabolismo
Estimulação Elétrica
Endocitose/genética
Canais de Potássio Éter-A-Go-Go/genética
Canais de Potássio Éter-A-Go-Go/metabolismo
Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos
Potenciais Pós-Sinápticos Excitadores/genética
Regulação da Expressão Gênica no Desenvolvimento/genética
Regulação da Expressão Gênica no Desenvolvimento/fisiologia
Técnicas In Vitro
Camundongos
Camundongos Transgênicos
Técnicas de Patch-Clamp
Proteína Vesicular 1 de Transporte de Glutamato/genética
Proteína Vesicular 1 de Transporte de Glutamato/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Early Growth Response Protein 2); 0 (Erg2 protein, rat); 0 (Ether-A-Go-Go Potassium Channels); 0 (Slc17a7 protein, mouse); 0 (Vesicular Glutamate Transport Protein 1); EC 3.5.1.50 (Dynamin I); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160603
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3804-15.2016


  4 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:27023174
[Au] Autor:Costas J; Carrera N; Alonso P; Gurriarán X; Segalàs C; Real E; López-Solà C; Mas S; Gassó P; Domènech L; Morell M; Quintela I; Lázaro L; Menchón JM; Estivill X; Carracedo Á
[Ad] Endereço:Grupo de Xenética Psiquiátrica, Instituto de Investigación Sanitaria de Santiago, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde, Santiago de Compostela, Spain.
[Ti] Título:Exon-focused genome-wide association study of obsessive-compulsive disorder and shared polygenic risk with schizophrenia.
[So] Source:Transl Psychiatry;6:e768, 2016 Mar 29.
[Is] ISSN:2158-3188
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primary analysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenic risk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association at the gene-based test was found at DNM3 (P=7.9 × 10(-5)), a gene involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value after removal of the major histocompatibility complex region (lowest P=2.3 × 10(-6), explaining 3.7% of the variance). The shared polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may be involved in risk to OCD. The shared polygenic risk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explaining epidemiological data on cross-disorder risk. This common etiology may have clinical implications.
[Mh] Termos MeSH primário: Dinamina III/genética
Éxons/genética
Herança Multifatorial
Transtorno Obsessivo-Compulsivo/genética
Esquizofrenia/genética
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
Feminino
Predisposição Genética para Doença
Estudo de Associação Genômica Ampla
Genótipo
Seres Humanos
Masculino
Polimorfismo de Nucleotídeo Único
Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160330
[St] Status:MEDLINE
[do] DOI:10.1038/tp.2016.34


  5 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
[PMID]:26784388
[Au] Autor:Zhang Z; Chen C; Guo W; Zheng S; Sun Z; Geng X
[Ad] Endereço:Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
[Ti] Título:DNM3 Attenuates Hepatocellular Carcinoma Growth by Activating P53.
[So] Source:Med Sci Monit;22:197-205, 2016 Jan 19.
[Is] ISSN:1643-3750
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Primary hepatocellular carcinoma is one of the most common malignant tumors in China and its mortality rate shows no sign at present of ceasing to rise. In our previous study, we found that the mRNA level of Dynamin3 (DNM3), a member of the Dynamin family, is significantly lower in hepatocellular carcinoma tissues than in non-tumor tissues. The aim of this study was to investigate the expression pattern and potential function of DNM3 in hepatocellular carcinoma. MATERIAL/METHODS: First, we determined the expression ofDNM3 in human hepatocellular carcinoma tissues and cell lines. We then studied the biological function of DNM3 on hepatocellular carcinoma cells by proliferation assay and colony formation assay. Flow cytometry was used to study the effect of DNM3 on cell cycle and apoptosis. RESULTS: Expression of DNM3 was significantly downregulated in hepatocellular carcinoma tissues and was associated with vein invasion and tumor metastasis. In addition, upregulation of DNM3 reduced hepatocellular carcinoma cell proliferation and colony formation, induced hepatocellular carcinoma cell G0/G1 phase arrest, and stimulated hepatocellular carcinoma cell apoptosis. We also found that DNM3 may exert its anti-proliferative effect through upregulating p53. CONCLUSIONS: Our findings suggest that DNM3 attenuates the proliferation and induces apoptosis of gastric cancer cells. Modulation of DNM3 may prove to be an efficient method of hepatocellular carcinoma treatment.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/patologia
Dinamina III/metabolismo
Neoplasias Hepáticas/patologia
Proteína Supressora de Tumor p53/metabolismo
[Mh] Termos MeSH secundário: Idoso
Apoptose/genética
Carcinoma Hepatocelular/genética
Pontos de Checagem do Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular
Dinamina III/genética
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Neoplasias Hepáticas/genética
Masculino
Meia-Idade
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Ensaio Tumoral de Célula-Tronco
Regulação para Cima/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 0 (Tumor Suppressor Protein p53); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160120
[St] Status:MEDLINE


  6 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26333682
[Au] Autor:Ashraf T; Collinson MN; Fairhurst J; Wang R; Wilson LC; Foulds N
[Ad] Endereço:Guy's Clinical Genetics Service, Guy's Hospital, London, United Kingdom.
[Ti] Título:Two further patients with the 1q24 deletion syndrome expand the phenotype: A possible role for the miR199-214 cluster in the skeletal features of the condition.
[So] Source:Am J Med Genet A;167A(12):3153-60, 2015 Dec.
[Is] ISSN:1552-4833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Submicroscopic deletions within chromosome 1q24q25 are associated with a syndromic phenotype of short stature, brachydactyly, learning difficulties, and facial dysmorphism. The critical region for the deletion phenotype has previously been narrowed to a 1.9 Mb segment containing 13 genes. We describe two further patients with 1q24 microdeletions and the skeletal phenotype, the first of whom has normal intellect, whereas the second has only mild learning impairment. The deletion in the first patient is very small and further narrows the critical interval for the striking skeletal aspects of this condition to a region containing only Dynamin 3 (DNM3) and two microRNAs that are harbored within intron 14 of this gene: miR199 and miR214. Mouse studies raise the possibility that these microRNAs may be implicated in the short stature and skeletal abnormalities of this microdeletion condition. The deletion in the second patient spans the previously reported critical region and indicates that the cognitive impairment may not always be as severe as previous reports suggest.
[Mh] Termos MeSH primário: Anormalidades Múltiplas/genética
Doenças do Desenvolvimento Ósseo/genética
Deleção Cromossômica
Cromossomos Humanos Par 1/genética
Dinamina III/genética
MicroRNAs/genética
[Mh] Termos MeSH secundário: Anormalidades Múltiplas/patologia
Adolescente
Adulto
Animais
Doenças do Desenvolvimento Ósseo/patologia
Braquidactilia/genética
Braquidactilia/patologia
Hibridização Genômica Comparativa
Feminino
Seres Humanos
Recém-Nascido
Deficiência Intelectual/genética
Deficiência Intelectual/patologia
Masculino
Camundongos
Fenótipo
Prognóstico
Síndrome
Gêmeos Monozigóticos/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN214 microRNA, human); 0 (MicroRNAs); 0 (mirn199 microRNA, human); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150904
[St] Status:MEDLINE
[do] DOI:10.1002/ajmg.a.37336


  7 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25827095
[Au] Autor:Calabrese B; Halpain S
[Ad] Endereço:Division of Biological Sciences, University of California San Diego, La Jolla, CA, United States; Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, CA, United States. Electronic address: bcalabrese@ucsd.edu.
[Ti] Título:Differential targeting of dynamin-1 and dynamin-3 to nerve terminals during chronic suppression of neuronal activity.
[So] Source:Mol Cell Neurosci;68:36-45, 2015 Sep.
[Is] ISSN:1095-9327
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neurons express three closely related dynamin genes. Dynamin 1 has long been implicated in the regulation of synaptic vesicle recycling in nerve terminals, and dynamins 2 and 3 were more recently shown also to contribute to synaptic vesicle recycling in specific and distinguishable ways. In cultured hippocampal neurons we found that chronic suppression of spontaneous network activity differentially regulated the targeting of endogenous dynamins 1 and 3 to nerve terminals, while dynamin 2 was unaffected. Specifically, when neural activity was chronically silenced for 1-2weeks by tetrodotoxin (TTX), the clustering of dynamin 1 at nerve terminals was reduced, while the clustering of dynamin 3 significantly increased. Moreover, dynamin 3 clustering was induced within hours by the sustained blockade of AMPA receptors, suggesting that AMPA receptors may function to prevent Dyn3 accumulation within nerve terminals. Clustering of dynamin 3 was induced by an antagonist of the calcium-dependent protein phosphatase calcineurin, but was not dependent upon intact actin filaments. TTX-induced clustering of Dyn3 occurred with a markedly slower time-course than the previously described clustering of synapsin 1. Potassium-induced depolarization rapidly de-clustered dynamin 3 from nerve terminals within minutes. These results, which have implications for homeostatic synapse restructuring, indicate that the three dynamins have evolved different regulatory mechanisms for trafficking to and from nerve terminals in response to changes in neural activity.
[Mh] Termos MeSH primário: Dinamina III/metabolismo
Dinamina I/metabolismo
Neurônios/citologia
Neurônios/metabolismo
Terminações Pré-Sinápticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Dinamina I/genética
Dinamina III/genética
Embrião de Mamíferos
Antagonistas de Aminoácidos Excitatórios/farmacologia
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Hipocampo/citologia
Imunossupressores/farmacologia
Neurônios/efeitos dos fármacos
Terminações Pré-Sinápticas/efeitos dos fármacos
Terminações Pré-Sinápticas/ultraestrutura
Transporte Proteico/efeitos dos fármacos
Transporte Proteico/genética
Quinoxalinas/farmacologia
Ratos
Ratos Wistar
Bloqueadores dos Canais de Sódio/farmacologia
Sinapses/efeitos dos fármacos
Sinapses/metabolismo
Sinapses/ultraestrutura
Sinaptossomos/metabolismo
Tacrolimo/análogos & derivados
Tacrolimo/farmacologia
Tetrodotoxina/farmacologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Excitatory Amino Acid Antagonists); 0 (Immunosuppressive Agents); 0 (Quinoxalines); 0 (Sodium Channel Blockers); 147336-22-9 (Green Fluorescent Proteins); 4368-28-9 (Tetrodotoxin); 62T278S1MX (FG 9041); AUF4U5NSJK (immunomycin); EC 3.5.1.50 (Dynamin I); EC 3.6.5.5 (Dynamin III); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150402
[St] Status:MEDLINE


  8 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25783003
[Au] Autor:Byers CE; Barylko B; Ross JA; Southworth DR; James NG; Taylor CA; Wang L; Collins KA; Estrada A; Waung M; Tassin TC; Huber KM; Jameson DM; Albanesi JP
[Ad] Endereço:Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States.
[Ti] Título:Enhancement of dynamin polymerization and GTPase activity by Arc/Arg3.1.
[So] Source:Biochim Biophys Acta;1850(6):1310-8, 2015 Jun.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The Activity-regulated cytoskeleton-associated protein, Arc, is an immediate-early gene product implicated in various forms of synaptic plasticity. Arc promotes endocytosis of AMPA type glutamate receptors and regulates cytoskeletal assembly in neuronal dendrites. Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission. METHODS: Enzymatic and turbidity assays are used in this study to monitor effects of Arc on dynamin activity and polymerization. Arc oligomerization is measured using a combination of approaches, including size exclusion chromatography, sedimentation analysis, dynamic light scattering, fluorescence correlation spectroscopy, and electron microscopy. RESULTS: We present evidence that bacterially-expressed His6-Arc facilitates the polymerization of dynamin 2 and stimulates its GTPase activity under physiologic conditions (37°C and 100mM NaCl). At lower ionic strength Arc also stabilizes pre-formed dynamin 2 polymers against GTP-dependent disassembly, thereby prolonging assembly-dependent GTP hydrolysis catalyzed by dynamin 2. Arc also increases the GTPase activity of dynamin 3, an isoform of implicated in dendrite remodeling, but does not affect the activity of dynamin 1, a neuron-specific isoform involved in synaptic vesicle recycling. We further show in this study that Arc (either His6-tagged or untagged) has a tendency to form large soluble oligomers, which may function as a scaffold for dynamin assembly and activation. CONCLUSIONS AND GENERAL SIGNIFICANCE: The ability of Arc to enhance dynamin polymerization and GTPase activation may provide a mechanism to explain Arc-mediated endocytosis of AMPA receptors and the accompanying effects on synaptic plasticity.
[Mh] Termos MeSH primário: Proteínas do Citoesqueleto/metabolismo
Dinaminas/metabolismo
Proteínas do Tecido Nervoso/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas do Citoesqueleto/química
Proteínas do Citoesqueleto/genética
Dinamina I/metabolismo
Dinamina II/metabolismo
Dinamina III/metabolismo
Dinaminas/química
Ativação Enzimática
Guanosina Trifosfato/metabolismo
Histidina/metabolismo
Seres Humanos
Hidrólise
Camundongos
Proteínas do Tecido Nervoso/química
Proteínas do Tecido Nervoso/genética
Oligopeptídeos/metabolismo
Polimerização
Ratos
Proteínas Recombinantes de Fusão/metabolismo
Cloreto de Sódio/química
Temperatura Ambiente
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Cytoskeletal Proteins); 0 (His-His-His-His-His-His); 0 (Nerve Tissue Proteins); 0 (Oligopeptides); 0 (Recombinant Fusion Proteins); 0 (activity regulated cytoskeletal-associated protein); 451W47IQ8X (Sodium Chloride); 4QD397987E (Histidine); 86-01-1 (Guanosine Triphosphate); EC 3.5.1.50 (Dynamin I); EC 3.6.5.5 (Dynamin II); EC 3.6.5.5 (Dynamin III); EC 3.6.5.5 (Dynamins)
[Em] Mês de entrada:1508
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150319
[St] Status:MEDLINE


  9 / 49 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25389292
[Au] Autor:Li C; Mpollo MS; Gonsalves CS; Tahara SM; Malik P; Kalra VK
[Ad] Endereço:From the Departments of Biochemistry and Molecular Biology and.
[Ti] Título:Peroxisome proliferator-activated receptor-α-mediated transcription of miR-199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1α.
[So] Source:J Biol Chem;289(52):36031-47, 2014 Dec 26.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endothelin-1, a potent vasoconstrictor, plays an important role in pulmonary hypertension (PH) in sickle cell disease (SCD). Our previous studies show that higher levels of placenta growth factor (PlGF), secreted by erythroid precursor cells, correlate with increased plasma levels of endothelin-1 (ET-1) and other functional markers of PH in SCD. PlGF-mediated ET-1 expression occurs via activation of hypoxia-inducible factor-1α (HIF-1α). However, relatively less is understood regarding how PlGF-mediated expression of HIF-1α and its downstream effector ET-1 are post-transcriptionally regulated. Herein, we show that PlGF treatment of endothelial cells resulted in reduced levels of miR-199a2, which targeted the 3'-UTR of HIF-1α mRNA and concomitantly led to augmented ET-1 expression. Plasma levels of miR-199a2 in SCD subjects were significantly lower with reciprocally high levels of plasma ET-1, unlike unaffected controls. This observation provided a molecular link between miR-199a2 and high levels of ET-1 in SCD. Furthermore, we show that miR-199a2 located in the DNM3os transcription unit was co-transcriptionally regulated by peroxisome proliferator-activated receptor α (PPARα). Binding of the latter to PPARα cis-elements in the promoter of DNM3os was demonstrated by promoter mutational analysis and ChIP. Additionally, we show that fenofibrate, a PPARα agonist, increased the expression of miR-199a2 and DNM3os; the former was responsible for reduced expression of HIF-1α and ET-1. In vivo studies of fenofibrate-fed Berkeley sickle mice resulted in increased levels of miR-199a2 and reduced levels of ET-1 in lung tissues. Our studies provide a potential therapeutic approach whereby fenofibrate-induced miR-199a2 expression can ameliorate PH by reduction of ET-1 levels.
[Mh] Termos MeSH primário: Endotelina-1/metabolismo
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
MicroRNAs/genética
PPAR alfa/fisiologia
Transcrição Genética
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Animais
Sequência de Bases
Sítios de Ligação
Células Cultivadas
Dinamina III/genética
Endotelina-1/genética
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Camundongos Endogâmicos C57BL
MicroRNAs/biossíntese
Dados de Sequência Molecular
Interferência de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Endothelin-1); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (MicroRNAs); 0 (PPAR alpha); 0 (mirn199 microRNA, human); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:161202
[Lr] Data última revisão:
161202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141113
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M114.600775


  10 / 49 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:24963135
[Au] Autor:Wu Y; O'Toole ET; Girard M; Ritter B; Messa M; Liu X; McPherson PS; Ferguson SM; De Camilli P
[Ad] Endereço:Department of Cell Biology, Yale University School of Medicine, New Haven, United States Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United
[Ti] Título:A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis.
[So] Source:Elife;3:e01621, 2014 Jun 24.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles ('bulk' endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME) is dramatically impaired, to gain insight into the poorly understood mechanisms underlying this process. Massive formation of bulk endosomes was not defective, but rather enhanced, in the absence of dynamin 1 and 3. The subsequent conversion of bulk endosomes into SVs was not accompanied by the accumulation of clathrin coated buds on their surface and this process proceeded even after further clathrin knock-down, suggesting its independence of clathrin. These findings support the existence of a pathway for SV reformation that bypasses the requirement for clathrin and dynamin 1/3 and that operates during intense synaptic activity.
[Mh] Termos MeSH primário: Clatrina/genética
Dinamina III/genética
Dinamina I/genética
Endocitose/genética
Neurônios/metabolismo
Vesículas Sinápticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Clatrina/deficiência
Dinamina I/deficiência
Dinamina III/deficiência
Embrião de Mamíferos
Endossomos/metabolismo
Exocitose/genética
Regulação da Expressão Gênica no Desenvolvimento
Técnicas de Silenciamento de Genes
Camundongos
Proteínas do Tecido Nervoso/genética
Proteínas do Tecido Nervoso/metabolismo
Neurônios/citologia
Cultura Primária de Células
Sinapses/genética
Sinapses/metabolismo
Transmissão Sináptica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Clathrin); 0 (Nerve Tissue Proteins); EC 3.5.1.50 (Dynamin I); EC 3.6.5.5 (Dynamin III)
[Em] Mês de entrada:1505
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140626
[St] Status:MEDLINE
[do] DOI:10.7554/eLife.01621



página 1 de 5 ir para página              
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde