Base de dados : MEDLINE
Pesquisa : D12.644.770 [Categoria DeCS]
Referências encontradas : 9063 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 907 ir para página                         

  1 / 9063 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28463106
[Au] Autor:Zhong Y; Wang J; Henderson MJ; Yang P; Hagen BM; Siddique T; Vogel BE; Deng HX; Fang S
[Ad] Endereço:Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, United States.
[Ti] Título:Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus.
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Over 170 different mutations in the gene encoding SOD1 all cause amyotrophic lateral sclerosis (ALS). Available studies have been primarily focused on the mechanisms underlying mutant SOD1 cytotoxicity. How cells defend against the cytotoxicity remains largely unknown. Here, we show that misfolding of ALS-linked SOD1 mutants and wild-type (wt) SOD1 exposes a normally buried nuclear export signal (NES)-like sequence. The nuclear export carrier protein CRM1 recognizes this NES-like sequence and exports misfolded SOD1 to the cytoplasm. Antibodies against the NES-like sequence recognize misfolded SOD1, but not native wt SOD1 both in vitro and in vivo. Disruption of the NES consensus sequence relocalizes mutant SOD1 to the nucleus, resulting in higher toxicity in cells, and severer impairments in locomotion, egg-laying, and survival in . Our data suggest that SOD1 mutants are removed from the nucleus by CRM1 as a defense mechanism against proteotoxicity of misfolded SOD1 in the nucleus.
[Mh] Termos MeSH primário: Transporte Ativo do Núcleo Celular
Carioferinas/metabolismo
Dobramento de Proteína
Receptores Citoplasmáticos e Nucleares/metabolismo
Superóxido Dismutase-1/metabolismo
Superóxido Dismutase-1/toxicidade
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Caenorhabditis elegans
Proteínas Mutantes/genética
Proteínas Mutantes/metabolismo
Proteínas Mutantes/toxicidade
Ligação Proteica
Sinais Direcionadores de Proteínas
Superóxido Dismutase-1/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Karyopherins); 0 (Mutant Proteins); 0 (Protein Sorting Signals); 0 (Receptors, Cytoplasmic and Nuclear); 0 (exportin 1 protein); EC 1.15.1.1 (Superoxide Dismutase-1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28451972
[Au] Autor:Nielsen H
[Ad] Endereço:Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, Bldg., 208, 3500 Kgs., Lyngby, Denmark. hnielsen@cbs.dtu.dk.
[Ti] Título:Predicting Secretory Proteins with SignalP.
[So] Source:Methods Mol Biol;1611:59-73, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SignalP is the currently most widely used program for prediction of signal peptides from amino acid sequences. Proteins with signal peptides are targeted to the secretory pathway, but are not necessarily secreted. After a brief introduction to the biology of signal peptides and the history of signal peptide prediction, this chapter will describe all the options of the current version of SignalP and the details of the output from the program. The chapter includes a case study where the scores of SignalP were used in a novel way to predict the functional effects of amino acid substitutions in signal peptides.
[Mh] Termos MeSH primário: Biologia Computacional/métodos
Sinais Direcionadores de Proteínas/fisiologia
Proteínas/química
Análise de Sequência de Proteína/métodos
Software
[Mh] Termos MeSH secundário: Algoritmos
Proteínas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Sorting Signals); 0 (Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-7015-5_6


  3 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29262359
[Au] Autor:Hamsanathan S; Anthonymuthu TS; Bageshwar UK; Musser SM
[Ad] Endereço:Department of Molecular and Cellular Medicine, College of Medicine, The Texas A&M Health Science Center, Texas A&M University, College Station, Texas.
[Ti] Título:A Hinged Signal Peptide Hairpin Enables Tat-Dependent Protein Translocation.
[So] Source:Biophys J;113(12):2650-2668, 2017 Dec 19.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Tat machinery catalyzes the transport of folded proteins across the bacterial cytoplasmic membrane and the thylakoid membrane in plants. Using fluorescence quenching and cross-linking approaches, we demonstrate that the Escherichia coli TatBC complex catalyzes insertion of a pre-SufI signal peptide hairpin that penetrates about halfway across the membrane bilayer. Analysis of 512 bacterial Tat signal peptides using secondary structure prediction and docking algorithms suggest that this hairpin interaction mode is generally conserved. An internal cross-link in the signal peptide that blocks transport but does not affect binding indicates that a signal peptide conformational change is required during translocation. These results suggest, to our knowledge, a novel hairpin-hinge model in which the signal peptide hairpin unhinges during movement of the mature domain across the membrane. Thus, in addition to enabling the necessary recognition, the interaction of Tat signal peptides with the receptor complex plays a critical role in the transport process itself.
[Mh] Termos MeSH primário: Produtos do Gene tat/química
Produtos do Gene tat/metabolismo
Sinais Direcionadores de Proteínas
[Mh] Termos MeSH secundário: Bicamadas Lipídicas/metabolismo
Modelos Moleculares
Conformação Proteica
Transporte Proteico
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, tat); 0 (Lipid Bilayers); 0 (Protein Sorting Signals); 059QF0KO0R (Water)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE


  4 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29240807
[Au] Autor:Rotwein P
[Ad] Endereço:Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, United States of America.
[Ti] Título:Diversification of the insulin-like growth factor 1 gene in mammals.
[So] Source:PLoS One;12(12):e0189642, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Insulin-like growth factor 1 (IGF1), a small, secreted peptide growth factor, is involved in a variety of physiological and patho-physiological processes, including somatic growth, tissue repair, and metabolism of carbohydrates, proteins, and lipids. IGF1 gene expression appears to be controlled by several different signaling cascades in the few species in which it has been evaluated, with growth hormone playing a major role by activating a pathway involving the Stat5b transcription factor. Here, genes encoding IGF1 have been evaluated in 25 different mammalian species representing 15 different orders and ranging over ~180 million years of evolutionary diversification. Parts of the IGF1 gene have been fairly well conserved. Like rat Igf1 and human IGF1, 21 of 23 other genes are composed of 6 exons and 5 introns, and all 23 also contain recognizable tandem promoters, each with a unique leader exon. Exon and intron lengths are similar in most species, and DNA sequence conservation is moderately high in orthologous exons and proximal promoter regions. In contrast, putative growth hormone-activated Stat5b-binding enhancers found in analogous locations in rodent Igf1 and in human IGF1 loci, have undergone substantial variation in other mammals, and a processed retro-transposed IGF1 pseudogene is found in the sloth locus, but not in other mammalian genomes. Taken together, the fairly high level of organizational and nucleotide sequence similarity in the IGF1 gene among these 25 species supports the contention that some common regulatory pathways had existed prior to the beginning of mammalian speciation.
[Mh] Termos MeSH primário: Fator de Crescimento Insulin-Like I/genética
Mamíferos/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sequência Conservada
Bases de Dados Genéticas
Regulação da Expressão Gênica
Seres Humanos
Fator de Crescimento Insulin-Like I/química
Sinais Direcionadores de Proteínas
Pseudogenes
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Sorting Signals); 67763-96-6 (Insulin-Like Growth Factor I)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189642


  5 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28747436
[Au] Autor:Siddiqui SS; Springer SA; Verhagen A; Sundaramurthy V; Alisson-Silva F; Jiang W; Ghosh P; Varki A
[Ad] Endereço:From the Center for Academic Research and Training in Anthropogeny (CARTA) and Glycobiology Research and Training Center (GRTC) and.
[Ti] Título:The Alzheimer's disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool.
[So] Source:J Biol Chem;292(37):15312-15320, 2017 09 15.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimer's disease (LOAD), an apparently human-specific post-reproductive disease. generates two splice variants: a full-length CD33M transcript produced primarily by the "LOAD-risk" allele and a shorter CD33m isoform lacking the sialic acid-binding domain produced primarily from the "LOAD-protective" allele. An SNP that modulates CD33 splicing to favor CD33m is associated with enhanced microglial activity. Individuals expressing more protective isoform accumulate less brain ß-amyloid and have a lower LOAD risk. How the CD33m isoform increases ß-amyloid clearance remains unknown. We report that the protection by the CD33m isoform may not be conferred by what it does but, rather, from what it cannot do. Analysis of blood neutrophils and monocytes and a microglial cell line revealed that unlike CD33M, the CD33m isoform does not localize to cell surfaces; instead, it accumulates in peroxisomes. Cell stimulation and activation did not mobilize CD33m to the surface. Thus, the CD33m isoform may neither interact directly with amyloid plaques nor engage in cell-surface signaling. Rather, production and localization of CD33m in peroxisomes is a way of diminishing the amount of CD33M and enhancing ß-amyloid clearance. We confirmed intracellular localization by generating a CD33m-specific monoclonal antibody. Of note, CD33 is the only Siglec with a peroxisome-targeting sequence, and this motif emerged by convergent evolution in toothed whales, the only other mammals with a prolonged post-reproductive lifespan. The allele that protects post-reproductive individuals from LOAD may have evolved by adaptive loss-of-function, an example of the less-is-more hypothesis.
[Mh] Termos MeSH primário: Doença de Alzheimer/genética
Predisposição Genética para Doença
Macrófagos/metabolismo
Microglia/metabolismo
Neutrófilos/metabolismo
Polimorfismo de Nucleotídeo Único
Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo
[Mh] Termos MeSH secundário: Alelos
Doença de Alzheimer/imunologia
Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Motivos de Aminoácidos
Proteínas de Bactérias/metabolismo
Proteínas de Bactérias/toxicidade
Linhagem Celular
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Membrana Celular/patologia
Seres Humanos
Lipopolissacarídeos/toxicidade
Ativação de Macrófagos/efeitos dos fármacos
Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Macrófagos/patologia
Microglia/citologia
Microglia/imunologia
Microglia/patologia
N-Formilmetionina Leucil-Fenilalanina/toxicidade
Proteínas do Tecido Nervoso/química
Proteínas do Tecido Nervoso/genética
Proteínas do Tecido Nervoso/metabolismo
Neuraminidase/metabolismo
Neuraminidase/toxicidade
Ativação de Neutrófilo/efeitos dos fármacos
Neutrófilos/efeitos dos fármacos
Neutrófilos/imunologia
Neutrófilos/patologia
Peroxissomos/efeitos dos fármacos
Peroxissomos/metabolismo
Peroxissomos/patologia
Filogenia
Domínios e Motivos de Interação entre Proteínas
Isoformas de Proteínas/química
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Sinais Direcionadores de Proteínas
Transporte Proteico/efeitos dos fármacos
Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/química
Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (CD33 protein, human); 0 (Lipopolysaccharides); 0 (Nerve Tissue Proteins); 0 (Protein Isoforms); 0 (Protein Sorting Signals); 0 (Sialic Acid Binding Ig-like Lectin 3); 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine); EC 3.2.1.18 (Neuraminidase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171230
[Lr] Data última revisão:
171230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.799346


  6 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28862756
[Au] Autor:Haßdenteufel S; Sicking M; Schorr S; Aviram N; Fecher-Trost C; Schuldiner M; Jung M; Zimmermann R; Lang S
[Ad] Endereço:Department of Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
[Ti] Título:hSnd2 protein represents an alternative targeting factor to the endoplasmic reticulum in human cells.
[So] Source:FEBS Lett;591(20):3211-3224, 2017 Oct.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recently, understanding of protein targeting to the endoplasmic reticulum (ER) was expanded by the discovery of multiple pathways that function in parallel to the signal recognition particle (SRP). Guided entry of tail-anchored proteins and SRP independent (SND) are two such targeting pathways described in yeast. So far, no human SND component is functionally characterized. Here, we report hSnd2 as the first constituent of the human SND pathway able to support substrate-specific protein targeting to the ER. Similar to its yeast counterpart, hSnd2 is assumed to function as a membrane-bound receptor preferentially targeting precursors carrying C-terminal transmembrane domains. Our genetic and physical interaction studies show that hSnd2 is part of a complex network of targeting and translocation that is dynamically regulated.
[Mh] Termos MeSH primário: Retículo Endoplasmático/metabolismo
Proteínas de Membrana/genética
Proteínas Nucleares/genética
Subunidades Proteicas/genética
Receptores Citoplasmáticos e Nucleares/genética
Receptores de Peptídeos/genética
Canais de Translocação SEC/genética
Proteínas de Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Regulação da Expressão Gênica
Células HeLa
Seres Humanos
Proteínas de Membrana/antagonistas & inibidores
Proteínas de Membrana/metabolismo
Proteínas Nucleares/metabolismo
Peptídeos/síntese química
Peptídeos/metabolismo
Ligação Proteica
Isoformas de Proteínas/antagonistas & inibidores
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Precursores de Proteínas/genética
Precursores de Proteínas/metabolismo
Sinais Direcionadores de Proteínas/genética
Subunidades Proteicas/metabolismo
Transporte Proteico
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Coelhos
Receptores Citoplasmáticos e Nucleares/metabolismo
Receptores de Peptídeos/metabolismo
Canais de Translocação SEC/metabolismo
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores
Proteínas de Saccharomyces cerevisiae/metabolismo
Partícula de Reconhecimento de Sinal
Transdução de Sinais
Especificidade por Substrato
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Membrane Proteins); 0 (Nuclear Proteins); 0 (Peptides); 0 (Protein Isoforms); 0 (Protein Precursors); 0 (Protein Sorting Signals); 0 (Protein Subunits); 0 (RNA, Small Interfering); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Receptors, Peptide); 0 (SEC Translocation Channels); 0 (Saccharomyces cerevisiae Proteins); 0 (Signal Recognition Particle); 0 (Snd2 protein, S cerevisiae); 0 (WRB protein, human); 0 (signal peptide receptor)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12831


  7 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28850829
[Au] Autor:Howard K; Cherezova L; DeMaster LK; Rose TM
[Ad] Endereço:Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA. Electronic address: kellie.howard@covance.com.
[Ti] Título:ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin ß1 for non-classical nuclear import.
[So] Source:Virology;511:152-164, 2017 Nov.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin ß1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype.
[Mh] Termos MeSH primário: Transporte Ativo do Núcleo Celular
Antígenos Nucleares/metabolismo
Interações Hospedeiro-Patógeno
Mapeamento de Interação de Proteínas
Rhadinovirus/fisiologia
Proteínas Virais/metabolismo
beta Carioferinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Antígenos Nucleares/genética
Macaca mulatta
Macaca nemestrina
Ligação Proteica
Sinais Direcionadores de Proteínas
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Nuclear); 0 (Protein Sorting Signals); 0 (Viral Proteins); 0 (beta Karyopherins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE


  8 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28847807
[Au] Autor:Wu S; Fagan RR; Uttamapinant C; Lifshitz LM; Fogarty KE; Ting AY; Melikian HE
[Ad] Endereço:Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01604.
[Ti] Título:The Dopamine Transporter Recycles via a Retromer-Dependent Postendocytic Mechanism: Tracking Studies Using a Novel Fluorophore-Coupling Approach.
[So] Source:J Neurosci;37(39):9438-9452, 2017 Sep 27.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Presynaptic reuptake, mediated by the dopamine (DA) transporter (DAT), terminates DAergic neurotransmission and constrains extracellular DA levels. Addictive and therapeutic psychostimulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neuropsychiatric disorders. These findings underscore that DAT is critical for DA neurotransmission and homeostasis. DAT surface availability is regulated acutely by endocytic trafficking, and considerable effort has been directed toward understanding mechanisms that govern DAT's plasma membrane expression and postendocytic fate. Multiple studies have demonstrated DAT endocytic recycling and enhanced surface delivery in response to various stimuli. Paradoxically, imaging studies have not detected DAT targeting to classic recycling endosomes, suggesting that internalized DAT targets to either degradation or an undefined recycling compartment. Here, we leveraged PRIME ( obe ncorporation ediated by nzyme) labeling to couple surface DAT directly to fluorophore, and tracked DAT's postendocytic itinerary in immortalized mesencephalic cells. Following internalization, DAT robustly targeted to retromer-positive endosomes, and DAT/retromer colocalization was observed in male mouse dopaminergic somatodendritic and terminal regions. Short hairpin RNA-mediated Vps35 knockdown revealed that DAT endocytic recycling requires intact retromer. DAT also targeted rab7-positive endosomes with slow, linear kinetics that were unaffected by either accelerating DAT internalization or binding a high-affinity cocaine analog. However, cocaine increased DAT exit from retromer-positive endosomes significantly. Finally, we found that the DAT carboxy-terminal PDZ-binding motif was required for DAT recycling and exit from retromer. These results define the DAT recycling mechanism and provide a unifying explanation for previous, seemingly disparate, DAT endocytic trafficking findings. The neuronal dopamine (DA) transporter (DAT) recaptures released DA and modulates DAergic neurotransmission, and a number of DAT coding variants have been reported in several DA-related disorders, including infantile parkinsonism, attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is also competitively inhibited by psychostimulants with high abuse potential. Therefore, mechanisms that acutely affect DAT availability will likely exert significant impact on both normal and pathological DAergic homeostasis. Here, we explore the cellular mechanisms that acutely control DAT surface expression. Our results reveal the intracellular mechanisms that mediate DAT endocytic recycling following constitutive and regulated internalization. In addition to shedding light on this critical process, these findings resolve conflict among multiple, seemingly disparate, previous reports on DAT's postendocytic fate.
[Mh] Termos MeSH primário: Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo
Endocitose
[Mh] Termos MeSH secundário: Animais
Membrana Celular/metabolismo
Proteínas da Membrana Plasmática de Transporte de Dopamina/química
Endossomos/metabolismo
Células HEK293
Seres Humanos
Masculino
Mesencéfalo/citologia
Camundongos
Camundongos Endogâmicos C57BL
Neurônios/metabolismo
Terminações Pré-Sinápticas/metabolismo
Sinais Direcionadores de Proteínas
Transporte Proteico
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dopamine Plasma Membrane Transport Proteins); 0 (Protein Sorting Signals)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171015
[Lr] Data última revisão:
171015
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3885-16.2017


  9 / 9063 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28838758
[Au] Autor:Damasceno TF; Dias RO; de Oliveira JR; Salinas RK; Juliano MA; Ferreira C; Terra WR
[Ad] Endereço:Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Avenida Professor Lineu Prestes, 748, São Paulo 05508-000, Brazil.
[Ti] Título:Active subsite properties, subsite residues and targeting to lysosomes or midgut lumen of cathepsins L from the beetle Tenebrio molitor.
[So] Source:Insect Biochem Mol Biol;89:17-30, 2017 Oct.
[Is] ISSN:1879-0240
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cathepsins L are the major digestive peptidases in the beetle Tenebrio molitor. Two digestive cathepsins L (TmCAL2 and TmCAL3) from it had their 3D structures solved. The aim of this paper was to study in details TmCAL3 specificity and properties and relate them to its 3D structure. Recombinant TmCAL3 was assayed with 64 oligopeptides with different amino acid replacements in positions P2, P1, P1' and P2'. Results showed that TmCAL3 S2 specificity differs from the human enzyme and that its specificities also explain why on autoactivation two propeptide residues remain in the enzyme. Data on free energy of binding and of activation showed that S1 and S2' are mainly involved in substrate binding, S1' acts in substrate binding and catalysis, whereas S2 is implied mainly in catalysis. Enzyme subsite residues were identified by docking with the same oligopeptide used for kinetics. The subsite hydrophobicities were calculated from the efficiency of hydrolysis of different amino acid replacements in the peptide and from docking data. The results were closer for S1 and S2' than for S1' and S2, indicating that the residue subsites that were more involved in transition state binding are different from those binding the substrate seen in docking. Besides TmCAL1-3, there are nine other cathepsins L, most of them more expressed at midgut. They are supposed to be directed to lysosomes by a Drosophila-like Lerp receptor and/or motifs in their prodomains. The mannose 6-phosphate lysosomal sorting machinery is absent from T. molitor transcriptome. Cathepsin L direction to midgut contents seems to depend on overexpression.
[Mh] Termos MeSH primário: Catepsina L/metabolismo
Tenebrio/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Catálise
Catepsina L/química
Trato Gastrointestinal/enzimologia
Interações Hidrofóbicas e Hidrofílicas
Proteínas de Insetos/química
Proteínas de Insetos/metabolismo
Lisossomos/enzimologia
Simulação de Acoplamento Molecular
Sinais Direcionadores de Proteínas
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insect Proteins); 0 (Protein Sorting Signals); EC 3.4.22.15 (Cathepsin L)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE


  10 / 9063 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28808133
[Au] Autor:Bowden KE; Wiese NS; Perwez T; Mohanty BK; Kushner SR
[Ad] Endereço:Department of Genetics, University of Georgia, Athens, Georgia, USA.
[Ti] Título:The -Encoded Truncated RNase PH Protein Inhibits RNase P Maturation of Pre-tRNAs with Short Leader Sequences in the Absence of RppH.
[So] Source:J Bacteriol;199(22), 2017 Nov 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNase PH, encoded by the gene, is a 3'→5' exoribonuclease that in participates primarily in the 3' maturation of pre-tRNAs and the degradation of rRNA in stationary-phase cells. Interestingly, the routinely used laboratory strains of MG1655 and W3110 have naturally acquired the allele, encoding a truncated catalytically inactive RNase PH protein which is widely assumed to be benign. Contrary to this assumption, we show that the -encoded Rph-1 protein inhibits RNase P-mediated 5'-end maturation of primary pre-tRNAs with leaders of <5 nucleotides in the absence of RppH, an RNA pyrophosphohydrolase. In contrast, RppH is not required for 5'-end maturation of endonucleolytically generated pre-tRNAs in the strain and for any tRNAs in Δ mutant or strains. We propose that the Rph-1 protein bound to the 3' end of the substrate creates a steric hindrance that in the presence of a triphosphate at the 5' end reduces the ability of RNase P to bind to the pre-tRNA. In this paper, we demonstrate that the mutation found in commonly used strains leads to the synthesis of a truncated functionally inactive RNase PH protein that interferes with the 5'-end maturation of specific tRNAs with short 5' leaders by RNase P in the absence of RppH, an RNA pyrophosphohydrolase that converts primary 5' triphosphates into 5' monophosphates. The data presented indicate that the presence of the triphosphate interferes with RNase P binding to the pre-tRNA.
[Mh] Termos MeSH primário: Hidrolases Anidrido Ácido/genética
Hidrolases Anidrido Ácido/metabolismo
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Exorribonucleases/genética
RNA de Transferência/metabolismo
Ribonuclease P/metabolismo
[Mh] Termos MeSH secundário: Endorribonucleases/genética
Endorribonucleases/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Exorribonucleases/metabolismo
Mutação
Sinais Direcionadores de Proteínas
Precursores de RNA/química
Precursores de RNA/genética
Precursores de RNA/metabolismo
Processamento Pós-Transcricional do RNA
RNA Bacteriano/genética
RNA Bacteriano/metabolismo
RNA de Transferência/química
RNA de Transferência/genética
Ribonuclease P/genética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (Protein Sorting Signals); 0 (RNA Precursors); 0 (RNA, Bacterial); 9014-25-9 (RNA, Transfer); EC 2.7.7.56 (ribonuclease PH); EC 3.1.- (Endoribonucleases); EC 3.1.- (Exoribonucleases); EC 3.1.26.5 (Ribonuclease P); EC 3.1.4.- (ribonuclease E); EC 3.6.- (Acid Anhydride Hydrolases); EC 3.6.1.- (RppH protein, E coli)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE



página 1 de 907 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