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[PMID]:28743825
[Au] Autor:Navarro Negredo P; Edgar JR; Wrobel AG; Zaccai NR; Antrobus R; Owen DJ; Robinson MS
[Ad] Endereço:Cambridge Institute for Medical Research, University of Cambridge, Cambridge, England, UK.
[Ti] Título:Contribution of the clathrin adaptor AP-1 subunit µ1 to acidic cluster protein sorting.
[So] Source:J Cell Biol;216(9):2927-2943, 2017 Sep 04.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acidic clusters act as sorting signals for packaging cargo into clathrin-coated vesicles (CCVs), and also facilitate down-regulation of MHC-I by HIV-1 Nef. To find acidic cluster sorting machinery, we performed a gene-trap screen and identified the medium subunit (µ1) of the clathrin adaptor AP-1 as a top hit. In µ1 knockout cells, intracellular CCVs still form, but acidic cluster proteins are depleted, although several other CCV components were either unaffected or increased, indicating that cells can compensate for long-term loss of AP-1. In vitro experiments showed that the basic patch on µ1 that interacts with the Nef acidic cluster also contributes to the binding of endogenous acidic cluster proteins. Surprisingly, µ1 mutant proteins lacking the basic patch and/or the tyrosine-based motif binding pocket could rescue the µ1 knockout phenotype completely. In contrast, these mutants failed to rescue Nef-induced down-regulation of MHC class I, suggesting a possible mechanism for attacking the virus while sparing the host cell.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Subunidades mu do Complexo de Proteínas Adaptadoras/metabolismo
Vesículas Revestidas por Clatrina/metabolismo
HIV-1/metabolismo
Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/química
Complexo 1 de Proteínas Adaptadoras/genética
Subunidades mu do Complexo de Proteínas Adaptadoras/química
Subunidades mu do Complexo de Proteínas Adaptadoras/genética
Sistemas CRISPR-Cas
Citometria de Fluxo
Técnicas de Silenciamento de Genes
Genótipo
Células HEK293
HIV-1/genética
Células HeLa
Antígenos de Histocompatibilidade Classe I/genética
Antígenos de Histocompatibilidade Classe I/metabolismo
Interações Hospedeiro-Patógeno
Seres Humanos
Modelos Moleculares
Mutação
Fenótipo
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Transporte Proteico
Relação Estrutura-Atividade
Fatores de Tempo
Transfecção
Produtos do Gene nef do Vírus da Imunodeficiência Humana/química
Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AP1M1 protein, human); 0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex mu Subunits); 0 (Histocompatibility Antigens Class I); 0 (nef Gene Products, Human Immunodeficiency Virus); 0 (nef protein, Human immunodeficiency virus 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201602058


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[PMID]:28501330
[Au] Autor:Cain MD; Salimi H; Gong Y; Yang L; Hamilton SL; Heffernan JR; Hou J; Miller MJ; Klein RS
[Ad] Endereço:Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, United States.
[Ti] Título:Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection.
[So] Source:J Neuroimmunol;308:118-130, 2017 Jul 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability. Following intranasal infection of both wild-type and IFN-induced protein with tetratricopeptide repeats 1 (IFIT1)-deficient mice, which fail to block TC83-specific RNA translation, virus spreads to the olfactory bulb and cortex via migration along axonal tracts of neurons originating from the olfactory neuroepithelium. Global dissemination of virus in the CNS by 2days post-infection (dpi) was associated with increased BBB permeability in the olfactory bulb, but not in the cortex or hindbrain, where permeability only increased after the recruitment of CX3CR1 and CCR2 mononuclear cells on 6 dpi, which corresponded with tight junction loss and claudin 5 redistribution. Importantly, despite higher levels of viral replication, similar results were obtained in IFIT1-deficient mice. These findings indicate that TC83 gains CNS access via anterograde axonal migration without directly altering BBB function and that mononuclear and endothelial cell interactions may underlie BBB disruption during alphavirus encephalitis.
[Mh] Termos MeSH primário: Infecções por Alphavirus/patologia
Barreira Hematoencefálica/fisiopatologia
Encéfalo/metabolismo
Encéfalo/virologia
Replicação Viral/fisiologia
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/genética
Complexo 1 de Proteínas Adaptadoras/metabolismo
Infecções por Alphavirus/genética
Animais
Animais Recém-Nascidos
Barreira Hematoencefálica/ultraestrutura
Barreira Hematoencefálica/virologia
Receptor 1 de Quimiocina CX3C
Permeabilidade Capilar/fisiologia
Células Cultivadas
Córtex Cerebral/citologia
Cricetinae
Modelos Animais de Doenças
Vírus da Encefalite Equina Venezuelana/fisiologia
Células Epiteliais/efeitos dos fármacos
Células Epiteliais/fisiologia
Células Epiteliais/ultraestrutura
Células Epiteliais/virologia
Regulação da Expressão Gênica/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Receptores de Quimiocinas/genética
Receptores de Quimiocinas/metabolismo
Fator de Necrose Tumoral alfa/farmacologia
Internalização do Vírus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (CX3C Chemokine Receptor 1); 0 (Cx3cr1 protein, mouse); 0 (Receptors, Chemokine); 0 (Tumor Necrosis Factor-alpha)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170515
[St] Status:MEDLINE


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[PMID]:28430827
[Au] Autor:Venugopal K; Werkmeister E; Barois N; Saliou JM; Poncet A; Huot L; Sindikubwabo F; Hakimi MA; Langsley G; Lafont F; Marion S
[Ad] Endereço:Centre d'Infection et d'Immunité de Lille, Université de Lille, Inserm U1019, CNRS UMR 8204, CHU Lille, Institut Pasteur de Lille, Lille, France.
[Ti] Título:Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and microneme proteins and in parasite division.
[So] Source:PLoS Pathog;13(4):e1006331, 2017 Apr.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, ß, µ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the µ1 subunit resulted in the mis-sorting of microneme proteins at the level of the Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also participates in the post-Golgi maturation process of preROP compartments into apically anchored club-shaped mature organelles. For this latter activity, our data indicate a specific functional relationship between TgAP1 and the Rab5A-positive endosome-like compartment. In addition, we unraveled an original role for TgAP1 in the regulation of parasite division. APµ1-depleted parasites undergo normal daughter cell budding and basal complex assembly but fail to segregate at the end of cytokinesis.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Proteínas de Protozoários/metabolismo
Toxoplasma/metabolismo
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/genética
Animais
Divisão Celular
Clatrina/genética
Clatrina/metabolismo
Citocinese
Endossomos/metabolismo
Expressão Gênica
Técnicas de Inativação de Genes
Complexo de Golgi/metabolismo
Espectrometria de Massas
Modelos Biológicos
Organelas/metabolismo
Transporte Proteico
Proteínas de Protozoários/genética
Toxoplasma/genética
Toxoplasma/ultraestrutura
Rede trans-Golgi/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (Clathrin); 0 (Protozoan Proteins)
[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:170422
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006331


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[PMID]:28369060
[Au] Autor:Mendoza-García P; Hugosson F; Fallah M; Higgins ML; Iwasaki Y; Pfeifer K; Wolfstetter G; Varshney G; Popichenko D; Gergen JP; Hens K; Deplancke B; Palmer RH
[Ad] Endereço:Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
[Ti] Título:The Zic family homologue Odd-paired regulates Alk expression in Drosophila.
[So] Source:PLoS Genet;13(4):e1006617, 2017 Apr.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) plays a critical role in the specification of founder cells (FCs) in the Drosophila visceral mesoderm (VM) during embryogenesis. Reporter gene and CRISPR/Cas9 deletion analysis reveals enhancer regions in and upstream of the Alk locus that influence tissue-specific expression in the amnioserosa (AS), the VM and the epidermis. By performing high throughput yeast one-hybrid screens (Y1H) with a library of Drosophila transcription factors (TFs) we identify Odd-paired (Opa), the Drosophila homologue of the vertebrate Zic family of TFs, as a novel regulator of embryonic Alk expression. Further characterization identifies evolutionarily conserved Opa-binding cis-regulatory motifs in one of the Alk associated enhancer elements. Employing Alk reporter lines as well as CRISPR/Cas9-mediated removal of regulatory elements in the Alk locus, we show modulation of Alk expression by Opa in the embryonic AS, epidermis and VM. In addition, we identify enhancer elements that integrate input from additional TFs, such as Binou (Bin) and Bagpipe (Bap), to regulate VM expression of Alk in a combinatorial manner. Taken together, our data show that the Opa zinc finger TF is a novel regulator of embryonic Alk expression.
[Mh] Termos MeSH primário: Proteínas de Drosophila/genética
Drosophila melanogaster/embriologia
Regulação da Expressão Gênica no Desenvolvimento
Proteínas de Homeodomínio/genética
Receptores Proteína Tirosina Quinases/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/genética
Complexo 1 de Proteínas Adaptadoras/metabolismo
Subunidades beta do Complexo de Proteínas Adaptadoras/genética
Subunidades beta do Complexo de Proteínas Adaptadoras/metabolismo
Animais
Animais Geneticamente Modificados
Sítios de Ligação
Sistemas CRISPR-Cas
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Embrião não Mamífero
Elementos Facilitadores Genéticos
Fatores de Transcrição Forkhead/genética
Fatores de Transcrição Forkhead/metabolismo
Proteínas de Homeodomínio/metabolismo
Regiões Promotoras Genéticas
Receptores Proteína Tirosina Quinases/metabolismo
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex beta Subunits); 0 (Bap protein, Drosophila); 0 (Drosophila Proteins); 0 (Forkhead Transcription Factors); 0 (Homeodomain Proteins); 0 (Opa protein, Drosophila); 0 (Transcription Factors); 0 (biniou protein, Drosophila); EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases); EC 2.7.10.1 (anaplastic lymphoma kinase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006617


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[PMID]:28240606
[Au] Autor:Bekerman E; Neveu G; Shulla A; Brannan J; Pu SY; Wang S; Xiao F; Barouch-Bentov R; Bakken RR; Mateo R; Govero J; Nagamine CM; Diamond MS; De Jonghe S; Herdewijn P; Dye JM; Randall G; Einav S
[Ti] Título:Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.
[So] Source:J Clin Invest;127(4):1338-1352, 2017 Apr 03.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells. Moreover, we found that multiple viruses, including dengue and Ebola, exploit AAK1 and GAK during entry and infectious virus production. In cultured cells, treatment with sunitinib and erlotinib, approved anticancer drugs that inhibit AAK1 or GAK activity, or with more selective compounds inhibited intracellular trafficking of HCV and multiple unrelated RNA viruses with a high barrier to resistance. In murine models of dengue and Ebola infection, sunitinib/erlotinib combination protected against morbidity and mortality. We validated sunitinib- and erlotinib-mediated inhibition of AAK1 and GAK activity as an important mechanism of antiviral action. Additionally, we revealed potential roles for additional kinase targets. These findings advance our understanding of virus-host interactions and establish a proof of principle for a repurposed, host-targeted approach to combat emerging viruses.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Antivirais/farmacologia
Cloridrato de Erlotinib/farmacologia
Indóis/farmacologia
Inibidores de Proteínas Quinases/farmacologia
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Complexo 2 de Proteínas Adaptadoras/metabolismo
Animais
Linhagem Celular Tumoral
Dengue/prevenção & controle
Dengue/virologia
Vírus da Dengue/efeitos dos fármacos
Vírus da Dengue/metabolismo
Avaliação Pré-Clínica de Medicamentos
Sinergismo Farmacológico
Ebolavirus/efeitos dos fármacos
Ebolavirus/metabolismo
Feminino
Doença pelo Vírus Ebola/prevenção & controle
Doença pelo Vírus Ebola/virologia
Hepacivirus/efeitos dos fármacos
Hepacivirus/metabolismo
Hepatite C/prevenção & controle
Hepatite C/virologia
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Masculino
Camundongos da Linhagem 129
Camundongos Endogâmicos C57BL
Transporte Proteico
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas Serina-Treonina Quinases/metabolismo
Internalização do Vírus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex 2); 0 (Antineoplastic Agents); 0 (Antiviral Agents); 0 (Indoles); 0 (Intracellular Signaling Peptides and Proteins); 0 (Protein Kinase Inhibitors); 0 (Pyrroles); DA87705X9K (Erlotinib Hydrochloride); EC 2.7.11.1 (AAK1 protein, human); EC 2.7.11.1 (GAK protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); V99T50803M (sunitinib)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE


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[PMID]:28235798
[Au] Autor:Dib K; Tikhonova IG; Ivetic A; Schu P
[Ad] Endereço:From the Max Planck Institute for Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany, k.dib@qub.ac.uk.
[Ti] Título:The cytoplasmic tail of L-selectin interacts with the adaptor-protein complex AP-1 subunit µ1A via a novel basic binding motif.
[So] Source:J Biol Chem;292(16):6703-6714, 2017 Apr 21.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:L-selectin regulates leukocyte adhesion and rolling along the endothelium. Proteins binding to the cytoplasmic tail of L-selectin regulate L-selectin functions. We used L-selectin cytoplasmic tail peptide pulldown assays combined with high sensitivity liquid chromatography/mass spectrometry to identify novel L-selectin tail-binding proteins. Incubation of the L-selectin tail with cell extracts from phorbol 12-myristate 13-acetate-stimulated Raw 264.7 macrophages resulted in the binding of µ1A of the clathrin-coated vesicle AP-1 complex. Furthermore, full-length GST-µ1A and the GST-µ1A C-terminal domain, but not the GST-µ1A N-terminal domain, bind to L-selectin tail peptide, and the intracellular pool of L-selectin colocalizes with AP-1 at the -Golgi network. We identified a novel basic protein motif consisting of a cluster of three dibasic residues ( RR , KK , and KK ) in the membrane-proximal domain of the L-selectin tail as well as a doublet of aspartic acid residues ( DD ) in the membrane-distal end of the L-selectin tail involved in µ1A binding. Stimulation of Raw 264.7 macrophages with PMA augmented the amount of µ1A associated with anti-L-selectin immunoprecipitates. However, full-length GST-µ1A did not bind to the phospho-L-selectin tail or phospho-mimetic S364D L-selectin tail. Accordingly, we propose that phosphorylation of µ1A is required for interaction with the L-selectin tail and that L-selectin tail phosphorylation may regulate this interaction Molecular docking of the L-selectin tail to µ1A was used to identify the µ1A surface domain binding the L-selectin tail and to explain how phosphorylation of the L-selectin tail abrogates µ1A interaction. Our findings indicate that L-selectin is transported constitutively by the AP-1 complex, leading to the formation of a -Golgi network reserve pool and that phosphorylation of the L-selectin tail blocks AP-1-dependent retrograde transport of L-selectin.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/química
Subunidades mu do Complexo de Proteínas Adaptadoras/química
Selectina L/química
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Ácido Aspártico/química
Cristalografia por Raios X
Citoplasma/metabolismo
Endotélio Vascular/metabolismo
Glutationa Transferase/metabolismo
Proteínas de Fluorescência Verde/metabolismo
Imunoprecipitação
Macrófagos/metabolismo
Camundongos
Simulação de Acoplamento Molecular
Monócitos/metabolismo
Fosforilação
Ligação Proteica
Domínios Proteicos
Proteômica
Células RAW 264.7
Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
Serina/química
Rede trans-Golgi/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex mu Subunits); 0 (Ap1m1 protein, mouse); 126880-86-2 (L-Selectin); 147336-22-9 (Green Fluorescent Proteins); 30KYC7MIAI (Aspartic Acid); 452VLY9402 (Serine); EC 2.5.1.18 (Glutathione Transferase); EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases); EC 2.7.11.1 (Ripk1 protein, mouse)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768598


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[PMID]:27974503
[Au] Autor:Hoya M; Yanguas F; Moro S; Prescianotto-Baschong C; Doncel C; de León N; Curto MÁ; Spang A; Valdivieso MH
[Ad] Endereço:Department of Microbiology and Genetics, Institute of Functional Biology and Genomics (IBFG), University of Salamanca, Consejo Superior de Investigaciones Científicas (CSIC), 37007, Spain.
[Ti] Título:Traffic Through the Trans-Golgi Network and the Endosomal System Requires Collaboration Between Exomer and Clathrin Adaptors in Fission Yeast.
[So] Source:Genetics;205(2):673-690, 2017 Feb.
[Is] ISSN:1943-2631
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Despite its biological and medical relevance, traffic from the Golgi to the plasma membrane (PM) is one of the least understood steps of secretion. Exomer is a protein complex that mediates the trafficking of certain cargoes from the trans-Golgi network/early endosomes to the PM in budding yeast. Here, we show that in Schizosaccharomyces pombe the Cfr1 and Bch1 proteins constitute the simplest form of an exomer. Cfr1 co-immunoprecipitates with Assembly Polypeptide adaptor 1 (AP-1), AP-2, and Golgi-localized, gamma-adaptin ear domain homology, ARF-binding (GGA) subunits, and cfr1 interacts genetically with AP-1 and GGA genes. Exomer-defective cells exhibit multiple mild defects, including alterations in the morphology of Golgi stacks and the distribution of the synaptobrevin-like Syb1 protein, carboxypeptidase missorting, and stress sensitivity. S. pombe apm1Δ cells exhibit a defect in trafficking through the early endosomes that is severely aggravated in the absence of exomer. apm1Δ cfr1Δ cells exhibit a dramatic disorganization of intracellular compartments, including massive accumulation of electron-dense tubulovesicular structures. While the trans-Golgi network/early endosomes are severely disorganized in the apm1Δ cfr1Δ strain, gga21Δ gga22Δ cfr1Δ cells exhibit a significant disturbance of the prevacuolar/vacuolar compartments. Our findings show that exomer collaborates with clathrin adaptors in trafficking through diverse cellular compartments, and that this collaboration is important to maintain their integrity. These results indicate that the effect of eliminating exomer is more pervasive than that described to date, and suggest that exomer complexes might participate in diverse steps of vesicle transport in other organisms.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Complexo 2 de Proteínas Adaptadoras/metabolismo
Proteínas Adaptadoras de Transporte Vesicular/genética
Endossomos/metabolismo
Proteínas de Schizosaccharomyces pombe/genética
Schizosaccharomyces/metabolismo
Rede trans-Golgi/metabolismo
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/genética
Complexo 2 de Proteínas Adaptadoras/genética
Proteínas Adaptadoras de Transporte Vesicular/metabolismo
Ligação Proteica
Transporte Proteico
Proteínas R-SNARE/genética
Proteínas R-SNARE/metabolismo
Schizosaccharomyces/genética
Proteínas de Schizosaccharomyces pombe/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex 2); 0 (Adaptor Proteins, Vesicular Transport); 0 (R-SNARE Proteins); 0 (Schizosaccharomyces pombe Proteins); 0 (Syb1 protein, S pombe); 0 (cfr1 protein, S pombe)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170530
[Lr] Data última revisão:
170530
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE
[do] DOI:10.1534/genetics.116.193458


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[PMID]:27541731
[Au] Autor:Wang JG; Feng C; Liu HH; Ge FR; Li S; Li HJ; Zhang Y
[Ad] Endereço:State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Tai'an, China.
[Ti] Título:HAPLESS13-Mediated Trafficking of STRUBBELIG Is Critical for Ovule Development in Arabidopsis.
[So] Source:PLoS Genet;12(8):e1006269, 2016 Aug.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Planar morphogenesis, a distinct feature of multicellular organisms, is crucial for the development of ovule, progenitor of seeds. Both receptor-like kinases (RLKs) such as STRUBBELIG (SUB) and auxin gradient mediated by PIN-FORMED1 (PIN1) play instructive roles in this process. Fine-tuned intercellular communications between different cell layers during ovule development demands dynamic membrane distribution of these cell-surface proteins, presumably through vesicle-mediated sorting. However, the way it's achieved and the trafficking routes involved are obscure. We report that HAPLESS13 (HAP13)-mediated trafficking of SUB is critical for ovule development. HAP13 encodes the µ subunit of adaptor protein 1 (AP1) that mediates protein sorting at the trans-Golgi network/early endosome (TGN/EE). The HAP13 mutant, hap13-1, is defective in outer integument growth, resulting in exposed nucellus accompanied with impaired pollen tube guidance and reception. SUB is mis-targeted in hap13-1. However, unlike that of PIN2, the distribution of PIN1 is independent of HAP13. Genetic interference of exocytic trafficking at the TGN/EE by specifically downregulating HAP13 phenocopied the defects of hap13-1 in SUB targeting and ovule development, supporting a key role of sporophytically expressed SUB in instructing female gametogenesis.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/genética
Proteínas de Arabidopsis/genética
Proteínas de Membrana Transportadoras/genética
Óvulo Vegetal/genética
Receptores Proteína Tirosina Quinases/genética
[Mh] Termos MeSH secundário: Arabidopsis/genética
Arabidopsis/crescimento & desenvolvimento
Proteínas de Arabidopsis/biossíntese
Endossomos/genética
Gametogênese Vegetal/genética
Regulação da Expressão Gênica de Plantas
Ácidos Indolacéticos/metabolismo
Proteínas de Domínio MADS/biossíntese
Proteínas de Domínio MADS/genética
Proteínas de Membrana Transportadoras/biossíntese
Óvulo Vegetal/crescimento & desenvolvimento
Desenvolvimento Vegetal/genética
Transporte Proteico/genética
Receptores Proteína Tirosina Quinases/biossíntese
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AP1 protein, Arabidopsis); 0 (AP1M2 protein, Arabidopsis); 0 (Adaptor Protein Complex 1); 0 (Arabidopsis Proteins); 0 (Indoleacetic Acids); 0 (MADS Domain Proteins); 0 (Membrane Transport Proteins); 0 (PIN1 protein, Arabidopsis); 0 (PIN2 protein, Arabidopsis); EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases); EC 2.7.10.1 (SUB protein, Arabidopsis)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160820
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006269


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[PMID]:27312011
[Au] Autor:Jiang J; Promchan K; Jiang H; Awasthi P; Marshall H; Harned A; Natarajan V
[Ad] Endereço:Laboratory of Molecular Cell Biology, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: jiangj2@mail.nih.gov.
[Ti] Título:Depletion of BBS Protein LZTFL1 Affects Growth and Causes Retinal Degeneration in Mice.
[So] Source:J Genet Genomics;43(6):381-91, 2016 Jun 20.
[Is] ISSN:1673-8527
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Bardet-Biedl syndrome (BBS) is a heterogeneous disease characterized by deficiencies in various organs that are caused by defects in genes involved in the genesis, structural maintenance, and protein trafficking of cilia. Leucine zipper transcription factor-like 1 (LZTFL1) has been identified as a BBS protein (BBS17), because patients with mutations in this gene exhibit the common BBS phenotypes. In this study, we generated a knockout mouse model to investigate the effects of LZTFL1 depletion. Lztfl1 knockout mice were born with low birth weight, reached similar weight to those of wild-type mice at 10 weeks of age, and later gained more weight than their wild-type counterparts. LZTFL1 was localized to the primary cilium of kidney cells, and the absence of LZTFL1 increased the ciliary localization of BBS9. Moreover, in the retinas of Lztfl1 knockout mice, the photoreceptor outer segment was shortened, the distal axoneme of photoreceptor connecting cilium was significantly enlarged, and rhodopsin was targeted to the outer nuclear layer. TUNEL assay showed that many of these abnormal photoreceptor cells in Lztfl1 knockout mice underwent apoptosis. Interestingly, the absence of LZTFL1 caused an abnormal increase of the adaptor protein complex 1 (AP1) in some photoreceptor cells. Based on these data, we conclude that LZTFL1 is a cilium protein and regulates animal weight and photoreceptor connecting cilium function probably by controlling microtubule assembly and protein trafficking in cilia.
[Mh] Termos MeSH primário: Síndrome de Bardet-Biedl/genética
Técnicas de Inativação de Genes
Crescimento e Desenvolvimento/genética
Degeneração Retiniana/genética
Fatores de Transcrição/deficiência
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Animais
Axonema/metabolismo
Peso Corporal/genética
Morte Celular
Cílios/metabolismo
Progressão da Doença
Rim/patologia
Camundongos
Camundongos Endogâmicos C57BL
Proteínas Associadas aos Microtúbulos/metabolismo
Fenótipo
Células Fotorreceptoras/metabolismo
Transporte Proteico
Retina/patologia
Degeneração Retiniana/metabolismo
Degeneração Retiniana/patologia
Rodopsina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (BBS9 protein, mouse); 0 (Lztfl1protein, mouse); 0 (Microtubule-Associated Proteins); 0 (Transcription Factors); 9009-81-8 (Rhodopsin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160618
[St] Status:MEDLINE


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[PMID]:27293189
[Au] Autor:Sannerud R; Esselens C; Ejsmont P; Mattera R; Rochin L; Tharkeshwar AK; De Baets G; De Wever V; Habets R; Baert V; Vermeire W; Michiels C; Groot AJ; Wouters R; Dillen K; Vints K; Baatsen P; Munck S; Derua R; Waelkens E; Basi GS; Mercken M; Vooijs M; Bollen M; Schymkowitz J; Rousseau F; Bonifacino JS; Van Niel G; De Strooper B; Annaert W
[Ad] Endereço:VIB Center for the Biology of Disease, KU Leuven, 3000 Leuven, Belgium; Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
[Ti] Título:Restricted Location of PSEN2/γ-Secretase Determines Substrate Specificity and Generates an Intracellular Aß Pool.
[So] Source:Cell;166(1):193-208, 2016 Jun 30.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:γ-Secretases are a family of intramembrane-cleaving proteases involved in various signaling pathways and diseases, including Alzheimer's disease (AD). Cells co-express differing γ-secretase complexes, including two homologous presenilins (PSENs). We examined the significance of this heterogeneity and identified a unique motif in PSEN2 that directs this γ-secretase to late endosomes/lysosomes via a phosphorylation-dependent interaction with the AP-1 adaptor complex. Accordingly, PSEN2 selectively cleaves late endosomal/lysosomal localized substrates and generates the prominent pool of intracellular Aß that contains longer Aß; familial AD (FAD)-associated mutations in PSEN2 increased the levels of longer Aß further. Moreover, a subset of FAD mutants in PSEN1, normally more broadly distributed in the cell, phenocopies PSEN2 and shifts its localization to late endosomes/lysosomes. Thus, localization of γ-secretases determines substrate specificity, while FAD-causing mutations strongly enhance accumulation of aggregation-prone Aß42 in intracellular acidic compartments. The findings reveal potentially important roles for specific intracellular, localized reactions contributing to AD pathogenesis.
[Mh] Termos MeSH primário: Doença de Alzheimer/patologia
Secretases da Proteína Precursora do Amiloide/análise
Peptídeos beta-Amiloides/metabolismo
Fragmentos de Peptídeos/metabolismo
Presenilina-2/análise
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Doença de Alzheimer/genética
Doença de Alzheimer/metabolismo
Motivos de Aminoácidos
Secretases da Proteína Precursora do Amiloide/metabolismo
Animais
Linhagem Celular Tumoral
Endossomos/química
Seres Humanos
Lisossomos/química
Camundongos
Presenilina-1/análise
Presenilina-1/química
Presenilina-1/genética
Presenilina-1/metabolismo
Presenilina-2/química
Presenilina-2/genética
Presenilina-2/metabolismo
Ratos
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex 1); 0 (Amyloid beta-Peptides); 0 (PSEN1 protein, human); 0 (PSEN2 protein, human); 0 (Peptide Fragments); 0 (Presenilin-1); 0 (Presenilin-2); 0 (amyloid beta-protein (1-42)); EC 3.4.- (Amyloid Precursor Protein Secretases)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170111
[Lr] Data última revisão:
170111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160614
[St] Status:MEDLINE



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