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Pesquisa : D12.776.543.990.150.500.100 [Categoria DeCS]
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[PMID]:28003333
[Au] Autor:Kadlecova Z; Spielman SJ; Loerke D; Mohanakrishnan A; Reed DK; Schmid SL
[Ad] Endereço:Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
[Ti] Título:Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2.
[So] Source:J Cell Biol;216(1):167-179, 2017 Jan 02.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The critical initiation phase of clathrin-mediated endocytosis (CME) determines where and when endocytosis occurs. Heterotetrameric adaptor protein 2 (AP2) complexes, which initiate clathrin-coated pit (CCP) assembly, are activated by conformational changes in response to phosphatidylinositol-4,5-bisphosphate (PIP2) and cargo binding at multiple sites. However, the functional hierarchy of interactions and how these conformational changes relate to distinct steps in CCP formation in living cells remains unknown. We used quantitative live-cell analyses to measure discrete early stages of CME and show how sequential, allosterically regulated conformational changes activate AP2 to drive both nucleation and subsequent stabilization of nascent CCPs. Our data establish that cargoes containing Yxxφ motif, but not dileucine motif, play a critical role in the earliest stages of AP2 activation and CCP nucleation. Interestingly, these cargo and PIP2 interactions are not conserved in yeast. Thus, we speculate that AP2 has evolved as a key regulatory node to coordinate CCP formation and cargo sorting and ensure high spatial and temporal regulation of CME.
[Mh] Termos MeSH primário: Complexo 2 de Proteínas Adaptadoras/metabolismo
Vesículas Revestidas por Clatrina/metabolismo
Clatrina/metabolismo
Invaginações Revestidas da Membrana Celular/metabolismo
Endocitose
Epitélio Pigmentado da Retina/metabolismo
[Mh] Termos MeSH secundário: Complexo 2 de Proteínas Adaptadoras/química
Complexo 2 de Proteínas Adaptadoras/genética
Subunidades alfa do Complexo de Proteínas Adaptadoras/genética
Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Subunidades mu do Complexo de Proteínas Adaptadoras/genética
Subunidades mu do Complexo de Proteínas Adaptadoras/metabolismo
Motivos de Aminoácidos
Linhagem Celular
Seres Humanos
Fosfatidilinositol 4,5-Difosfato/metabolismo
Ligação Proteica
Conformação Proteica
Estabilidade Proteica
Transporte Proteico
Proteínas Serina-Treonina Quinases/metabolismo
Interferência de RNA
Transdução de Sinais
Relação Estrutura-Atividade
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 2); 0 (Adaptor Protein Complex alpha Subunits); 0 (Adaptor Protein Complex mu Subunits); 0 (Clathrin); 0 (Phosphatidylinositol 4,5-Diphosphate); 0 (adaptor protein complex 2, alpha 2 subunit); 0 (adaptor protein complex 2, mu 1 subunit); EC 2.7.11.1 (AAK1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201608071


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[PMID]:27165221
[Au] Autor:Poorhosseini SM; Hashemi M; Alipour Olyaei N; Izadi A; Moslemi E; Ravesh Z; Hashemi-Gorji F; Kheiri HR; Yassaee VR
[Ad] Endereço:Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail: v.yassaee-grc@sbmu.ac.ir.
[Ti] Título:New Gene Profiling in Determination of Breast Cancer Recurrence and Prognosis in Iranian Women.
[So] Source:Asian Pac J Cancer Prev;17(S3):155-60, 2016.
[Is] ISSN:2476-762X
[Cp] País de publicação:Thailand
[La] Idioma:eng
[Ab] Resumo:Breast cancer (BC) is the second most common cancer in the world and by far the most frequent cancer among women, with an estimated 1.67 million new cancer cases diagnosed in 2012 (25% of all cancers). Polygene expression analysis is used to predict the prognosis and determine the most appropriate treatment regimen. The objective of this study was to examine the gene expression profiles of SIRT3, HRAS, LSP1, SCUBE2 and AP2A2 in Iranian women with BC.A total of 136 patients including healthy controls were categorized into three groups based on the relapse of the disease. Expression of desired genes in formalin-fixed, paraffin embedded tissues collected from all groups of participants was analyzed via the RT PCR method. RNA extraction and cDNA synthesis were performed then real-time quantitative PCR was carried out. Gene expression analysis revealed that the expression of SIRT3 was equal among patient and control groups. LSP1 was down regulated in all patient groups relative to controls but reduced expression in the metastatic group relative to the non-metastatic one was not significant. HRAS was significantly overexpressed in total and metastatic tumor samples versus normal but not in non-metastatic cases. SCUBE2 expression showed significant over-expression in both overall tumor samples and the non-metastatic group as compared to normal tissues. Gene expression level of AP2A2 in all groups was not detectable. Our data are compatible with a tumor suppressor role of LSP1 related to potential prognostic factor for tumor recurrence and outcome. This study for the first time assayed the prognostic value and changes in the expression of SIRT3, LSP1, HRAS, SCUBE2 and AP2A2 genes in women with breast cancer in the Iranian population and findings confirmed potential biomarker and prognostic capability of these genes. Such expression profiling data can critically improve prognosis and treatment decisions in cancer patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Neoplasias da Mama/genética
Perfilação da Expressão Gênica
Recidiva Local de Neoplasia/diagnóstico
[Mh] Termos MeSH secundário: Complexo 2 de Proteínas Adaptadoras/genética
Subunidades alfa do Complexo de Proteínas Adaptadoras/genética
Neoplasias da Mama/patologia
Estudos de Casos e Controles
Feminino
Seguimentos
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Incidência
Irã (Geográfico)/epidemiologia
Proteínas de Membrana/genética
Proteínas dos Microfilamentos/genética
Meia-Idade
Recidiva Local de Neoplasia/epidemiologia
Recidiva Local de Neoplasia/genética
Prognóstico
Proteínas Proto-Oncogênicas p21(ras)/genética
Sirtuína 3/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex 2); 0 (Adaptor Protein Complex alpha Subunits); 0 (Biomarkers, Tumor); 0 (LSP1 protein, human); 0 (Membrane Proteins); 0 (Microfilament Proteins); 0 (SCUBE2 protein, human); 0 (adaptor protein complex 2, alpha 2 subunit); EC 3.5.1.- (SIRT3 protein, human); EC 3.5.1.- (Sirtuin 3); EC 3.6.5.2 (HRAS protein, human); EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170311
[Lr] Data última revisão:
170311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160512
[St] Status:MEDLINE


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[PMID]:26822536
[Au] Autor:Shimada A; Yamaguchi A; Kohda D
[Ad] Endereço:Division of Structural Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
[Ti] Título:Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 µ homology domain.
[So] Source:Sci Rep;6:19565, 2016 Jan 29.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their µ homology domains (µHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity µHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal µHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 µHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the µHD, which is distinct from those of other distantly related µHD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the µHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in µHD binding.
[Mh] Termos MeSH primário: Proteínas de Transporte/química
Proteínas de Transporte/metabolismo
Homologia Estrutural de Proteína
[Mh] Termos MeSH secundário: Subunidades alfa do Complexo de Proteínas Adaptadoras/química
Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Proteínas Adaptadoras de Transdução de Sinal/química
Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Motivos de Aminoácidos
Sequência de Aminoácidos
Aminoácidos/metabolismo
Sítios de Ligação
Calorimetria
Cristalografia por Raios X
Seres Humanos
Ligantes
Modelos Moleculares
Ligação Proteica
Domínios Proteicos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex alpha Subunits); 0 (Adaptor Proteins, Signal Transducing); 0 (Amino Acids); 0 (Carrier Proteins); 0 (EPS15 protein, human); 0 (Ligands); 0 (SGIP1 protein, human)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160130
[St] Status:MEDLINE
[do] DOI:10.1038/srep19565


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[PMID]:26370500
[Au] Autor:Pham K; Shimoni R; Charnley M; Ludford-Menting MJ; Hawkins ED; Ramsbottom K; Oliaro J; Izon D; Ting SB; Reynolds J; Lythe G; Molina-Paris C; Melichar H; Robey E; Humbert PO; Gu M; Russell SM
[Ad] Endereço:Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia Centre for Micro-Photonics, Faculty of Science, Engineering, and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
[Ti] Título:Asymmetric cell division during T cell development controls downstream fate.
[So] Source:J Cell Biol;210(6):933-50, 2015 Sep 14.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and α-Adaptin. ACD occurs specifically during the ß-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the ß-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal.
[Mh] Termos MeSH primário: Divisão Celular Assimétrica
Proliferação Celular
Timócitos/metabolismo
Timo/metabolismo
[Mh] Termos MeSH secundário: Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Animais
Comunicação Celular
Morte Celular
Diferenciação Celular
Polaridade Celular
Células Cultivadas
Microambiente Celular
Técnicas de Cocultura
Peptídeos e Proteínas de Sinalização Intracelular/deficiência
Peptídeos e Proteínas de Sinalização Intracelular/genética
Proteínas de Membrana/metabolismo
Camundongos Endogâmicos C57BL
Camundongos Knockout
Modelos Imunológicos
Proteínas do Tecido Nervoso/metabolismo
Fosforilação
Proteína Quinase C/metabolismo
Receptores CXCR4/metabolismo
Transdução de Sinais
Células Estromais/imunologia
Células Estromais/metabolismo
Timócitos/imunologia
Timo/citologia
Timo/imunologia
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex alpha Subunits); 0 (CXCR4 protein, human); 0 (Intracellular Signaling Peptides and Proteins); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Numb protein, mouse); 0 (Receptors, CXCR4); 0 (scribble protein, mouse); EC 2.7.11.13 (PKC-3 protein); EC 2.7.11.13 (Protein Kinase C)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150916
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201502053


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[PMID]:25966562
[Au] Autor:Gu X; Song R; Chen Z; Yuan W
[Ti] Título:[The expression and significance of adaptin-2 in mice cochlea].
[So] Source:Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi;29(1):83-5, 2015 Jan.
[Is] ISSN:1001-1781
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To investigate the expression of adaptin-2(AP-2) in mice cochlea and to discuss the probable role in the endocytosis of hair cells. METHOD: Laser scanning confocal microscopy and immune-fluroscence histochemistry were performed in this study. RESULT: In mature mice cochlea, the immunoreactivity for AP-2 was found in the inner hair cells cytoplasm. This protein mainly expressed in the hair cells basal part and nearby the ribbon synapse. CONCLUSION: AP-2 protein mainly expressed in the hair cells synaptic activity zone , which suggested that AP-2 could play an important role in the synaptic vesicle endocytosis. This finding built the foundation for the further research involved in the physiological and pathological role of AP-2.
[Mh] Termos MeSH primário: Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Células Ciliadas Auditivas Internas/metabolismo
[Mh] Termos MeSH secundário: Animais
Cóclea
Células Ciliadas Auditivas
Camundongos
Microscopia Confocal
Sinapses
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Protein Complex alpha Subunits)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:150513
[Lr] Data última revisão:
150513
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150514
[St] Status:MEDLINE


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[PMID]:25941814
[Au] Autor:Ding X; Ma M; Teng J; Shao F; Teng RK; Zhou S; Zhang Y; Wu E; Wang X
[Ti] Título:Numb induces e-cadherin adhesion dissolution, cytoskeleton reorganization, and migration in tubular epithelial cells contributing to renal fibrosis.
[So] Source:Curr Mol Med;15(4):368-79, 2015.
[Is] ISSN:1875-5666
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Numb, an endocytic protein, is involved in both neural differentiation and protein post-endocytic trafficking. Although negative Numb expression has been linked to human mammary carcinomas, little is known about its expression and functions in other diseases. In the present study, we observed that Numb is expressed in renal tubule epithelia and its expression is increased in the fibrotic kidney in vivo. We determined that in proximal tubular epithelial cells (NRK52E cells), TGF-ß1 induces the expression of Numb and ectopic expression of Numb leads to dissolution of E-cadherin adhesion, reorganization of cytoskeleton, activation of Rac1 and Cdc42, and enhancement of migration. Either knockdown of α-adaptin or overexpression of Numb asparagine-proline-phenylalanine (NPF) mutant interferes with AP-2 dependent endocytosis and rescues Ecadherin level in NRK52E cells. Moreover, knockdown of integrin ß1 or α-adaptin, and overexpression of a Numb dominant-negative form (Numb phosphotyrosine binding [PTB] domain) impair integrin endocytosis, and markedly inhibit Numb-induced cell migration and activation of Rac1 and Cdc42. Taken together, our work identifies Numb as an important player in renal fibrosis, by regulating epithelial-to-mesenchymal transition (EMT) process including E-cadherin adhesion dissolution, actin reorganization, and migration enhancement in NRK52E cells.
[Mh] Termos MeSH primário: Caderinas/metabolismo
Movimento Celular/genética
Transição Epitelial-Mesenquimal/fisiologia
Fibrose/patologia
Peptídeos e Proteínas de Sinalização Intracelular/genética
[Mh] Termos MeSH secundário: Complexo 2 de Proteínas Adaptadoras/metabolismo
Subunidades alfa do Complexo de Proteínas Adaptadoras/genética
Animais
Adesão Celular
Linhagem Celular
Citoesqueleto
Endocitose/genética
Endocitose/fisiologia
Ativação Enzimática
Células Epiteliais/metabolismo
Transição Epitelial-Mesenquimal/genética
Integrina beta1/genética
Túbulos Renais/citologia
Túbulos Renais/metabolismo
Túbulos Renais/patologia
Masculino
Interferência de RNA
RNA Interferente Pequeno
Ratos
Ratos Sprague-Dawley
Fator de Crescimento Transformador beta1/metabolismo
Proteína cdc42 de Ligação ao GTP/metabolismo
Proteínas rac1 de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex 2); 0 (Adaptor Protein Complex alpha Subunits); 0 (Cadherins); 0 (Integrin beta1); 0 (Intracellular Signaling Peptides and Proteins); 0 (RNA, Small Interfering); 0 (Transforming Growth Factor beta1); 0 (numb protein, rat); EC 3.6.1.- (Rac1 protein, rat); EC 3.6.5.2 (cdc42 GTP-Binding Protein); EC 3.6.5.2 (rac1 GTP-Binding Protein)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150506
[St] Status:MEDLINE


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[PMID]:24662566
[Au] Autor:Kasprowicz J; Kuenen S; Swerts J; Miskiewicz K; Verstreken P
[Ad] Endereço:VIB Center for the Biology of Disease, 2 Laboratory of Neuronal Communication, Department for Human Genetics, and 3 Leuven Institute for Neurodegenerative Diseases, KU Leuven, 3000 Leuven, Belgium.
[Ti] Título:Dynamin photoinactivation blocks Clathrin and α-adaptin recruitment and induces bulk membrane retrieval.
[So] Source:J Cell Biol;204(7):1141-56, 2014 Mar 31.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dynamin is a well-known regulator of synaptic endocytosis. Temperature-sensitive dynamin (shi(ts1)) mutations in Drosophila melanogaster or deletion of some of the mammalian Dynamins causes the accumulation of invaginated endocytic pits at synapses, sometimes also on bulk endosomes, indicating impaired membrane scission. However, complete loss of dynamin function has not been studied in neurons in vivo, and whether Dynamin acts in different aspects of synaptic vesicle formation remains enigmatic. We used acute photoinactivation and found that loss of Dynamin function blocked membrane recycling and caused the buildup of huge membrane-connected cisternae, in contrast to the invaginated pits that accumulate in shi(ts1) mutants. Moreover, photoinactivation of Dynamin in shi(ts1) animals converted these pits into bulk cisternae. Bulk membrane retrieval has also been seen upon Clathrin photoinactivation, and superresolution imaging indicated that acute Dynamin photoinactivation blocked Clathrin and α-adaptin relocalization to synaptic membranes upon nerve stimulation. Hence, our data indicate that Dynamin is critically involved in the stabilization of Clathrin- and AP2-dependent endocytic pits.
[Mh] Termos MeSH primário: Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Membrana Celular/metabolismo
Clatrina/metabolismo
Proteínas de Drosophila/fisiologia
Drosophila melanogaster/citologia
Dinaminas/fisiologia
[Mh] Termos MeSH secundário: Complexo 2 de Proteínas Adaptadoras/metabolismo
Animais
Membrana Celular/ultraestrutura
Células Cultivadas
Endocitose
Fluoresceína/química
Larva/citologia
Neurônios/fisiologia
Neurônios/ultraestrutura
Processos Fotoquímicos
Transporte Proteico
Vesículas Sinápticas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex 2); 0 (Adaptor Protein Complex alpha Subunits); 0 (Clathrin); 0 (Drosophila Proteins); EC 3.6.5.5 (Dynamins); EC 3.6.5.5 (shibire protein, Drosophila); TPY09G7XIR (Fluorescein)
[Em] Mês de entrada:1405
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140326
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201310090


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[PMID]:24399846
[Au] Autor:Alazami AM; Hijazi H; Kentab AY; Alkuraya FS
[Ad] Endereço:Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
[Ti] Título:NECAP1 loss of function leads to a severe infantile epileptic encephalopathy.
[So] Source:J Med Genet;51(4):224-8, 2014 Apr.
[Is] ISSN:1468-6244
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Epileptic encephalopathy is a broad clinical category that is highly heterogeneous genetically. OBJECTIVE: To describe a multiplex extended consanguineous family that defines a molecularly novel subtype of early infantile epileptic encephalopathy. METHODS: Autozygosity mapping and exome sequencing for the identification of the causal mutation. This was followed by expression analysis of the candidate gene. RESULTS: In an extended multigenerational family with six affected individuals, a single novel disease locus was identified on chromosome 12p13.31-p13.2. Within that locus, the only deleterious novel exomic variant was a homozygous truncating mutation in NECAP1, encoding a clathrin-accessory protein. The mutation was confirmed to trigger nonsense-mediated decay. Consistent with previous reports, we show that NECAP1 is highly enriched in the central nervous system. CONCLUSIONS: NECAP1 is known to regulate clathrin-mediated endocytosis in synapses. The mutation we report here links for the first time this trafficking pathway in early infantile epileptic encephalopathy.
[Mh] Termos MeSH primário: Subunidades alfa do Complexo de Proteínas Adaptadoras/genética
Proteínas de Membrana/genética
Mutação/genética
Espasmos Infantis/genética
[Mh] Termos MeSH secundário: Animais
Encéfalo/metabolismo
Encéfalo/patologia
Criança
Análise Mutacional de DNA
Família
Evolução Fatal
Feminino
Loci Gênicos/genética
Homozigoto
Seres Humanos
Lactente
Masculino
Camundongos
Linhagem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex alpha Subunits); 0 (Membrane Proteins); 0 (NECAP1 protein, human); 0 (NECAP1 protein, mouse)
[Em] Mês de entrada:1411
[Cu] Atualização por classe:140318
[Lr] Data última revisão:
140318
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140109
[St] Status:MEDLINE
[do] DOI:10.1136/jmedgenet-2013-102030


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[PMID]:23733933
[Au] Autor:Park M; Song K; Reichardt I; Kim H; Mayer U; Stierhof YD; Hwang I; Jürgens G
[Ad] Endereço:Entwicklungsgenetik and Microscopy, Zentrum für Molekularbiologie der Pflanzen (ZMBP), University of Tübingen, 72076 Tübingen, Germany.
[Ti] Título:Arabidopsis µ-adaptin subunit AP1M of adaptor protein complex 1 mediates late secretory and vacuolar traffic and is required for growth.
[So] Source:Proc Natl Acad Sci U S A;110(25):10318-23, 2013 Jun 18.
[Is] ISSN:1091-6490
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adaptor protein (AP) complexes are the predominant coat proteins of membrane vesicles in post-Golgi trafficking of mammalian cells. Each AP complex contains a specific medium subunit, µ-adaptin, that selects cargo proteins bearing sequence-specific sorting motifs. Much less is known about the AP complexes and their µ subunits in plants. Because of uncertain homology, the µ-adaptins of Arabidopsis have been designated muA through muD [Happel et al. (2004) Plant J 37(5):678-693]. Furthermore, only muD has been assigned to a specific AP complex, AP-3, involved in Golgi-vacuolar trafficking [Niihama et al. (2009) Plant Cell Physiol 50(12):2057-2068, Zwiewka et al. (2011) Cell Res 21(12):1711-1722, and Wolfenstetter et al. (2012) Plant Cell 24(1):215-232]. In contrast, the µ subunit of neither the post-Golgi trafficking AP-1 complex nor the endocytic AP-2 complex has been identified. Here, we report the functional analysis of redundant AP-1 µ-adaptins AP1M1 (also known as muB1) and AP1M2 (also known as muB2). Coimmunoprecipitation revealed that both AP1M2 and its less strongly expressed isoform AP1M1 are complexed with the large subunit γ-adaptin of AP-1. In addition, AP1M2 was localized at or near the trans-Golgi network. Knockout mutations of AP1M2 impaired pollen function and arrested plant growth whereas the ap1m1 ap1m2 double mutant was nearly pollen-lethal. At the cellular level, the absence of AP1M2 entailed inhibition of multiple trafficking pathways from the trans-Golgi network to the vacuole and to the plasma membrane in interphase and to the plane of cell division in cytokinesis. Thus, AP-1 is crucial in post-Golgi trafficking in plant cells and required for cell division and plant growth.
[Mh] Termos MeSH primário: Complexo 1 de Proteínas Adaptadoras/metabolismo
Subunidades mu do Complexo de Proteínas Adaptadoras/metabolismo
Proteínas de Arabidopsis/metabolismo
Arabidopsis/crescimento & desenvolvimento
Arabidopsis/genética
Transporte Proteico/fisiologia
[Mh] Termos MeSH secundário: Complexo 1 de Proteínas Adaptadoras/genética
Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Subunidades gama do Complexo de Proteínas Adaptadoras/metabolismo
Subunidades mu do Complexo de Proteínas Adaptadoras/genética
Arabidopsis/metabolismo
Proteínas de Arabidopsis/genética
Membrana Celular/fisiologia
Membrana Celular/ultraestrutura
Citocinese/fisiologia
Complexo de Golgi/metabolismo
Complexo de Golgi/ultraestrutura
Interfase/fisiologia
Microscopia Eletrônica de Transmissão
Mutagênese Insercional
Vesículas Secretórias/metabolismo
Vesículas Secretórias/ultraestrutura
Vacúolos/metabolismo
Vacúolos/ultraestrutura
Rede trans-Golgi/metabolismo
Rede trans-Golgi/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AP1M1 protein, Arabidopsis); 0 (AP1M2 protein, Arabidopsis); 0 (Adaptor Protein Complex 1); 0 (Adaptor Protein Complex alpha Subunits); 0 (Adaptor Protein Complex gamma Subunits); 0 (Adaptor Protein Complex mu Subunits); 0 (Arabidopsis Proteins); 0 (adaptor protein complex 1, mu 1 subunit); 0 (adaptor protein complex 1, mu 2 subunit)
[Em] Mês de entrada:1309
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130605
[St] Status:MEDLINE
[do] DOI:10.1073/pnas.1300460110


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[PMID]:23640057
[Au] Autor:Meng J; Wang J; Lawrence GW; Dolly JO
[Ad] Endereço:International Centre for Neurotherapeutics, Dublin City University, Glasnevin, Dublin 9, Ireland.
[Ti] Título:Molecular components required for resting and stimulated endocytosis of botulinum neurotoxins by glutamatergic and peptidergic neurons.
[So] Source:FASEB J;27(8):3167-80, 2013 Aug.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteins responsible for basal and stimulated endocytosis in nerves containing small clear synaptic vesicles (SCSVs) or large dense-core vesicles (LDCVs) are revealed herein, using probes that exploit surface-exposed vesicle proteins as acceptors for internalization. Basal uptake of botulinum neurotoxins (BoNTs) by both SCSV-releasing cerebellar granule neurons (CGNs) and LDCV-enriched trigeminal ganglionic neurons (TGNs) was found to require protein acceptors and acidic compartments. In addition, dynamin, clathrin, adaptor protein complex-2 (AP2), and amphiphysin contribute to the depolarization-evoked entry. For fast recycling of SCSVs, knockdown and knockout strategies demonstrated that CGNs use predominantly dynamin 1, whereas isoform 2 and, to a smaller extent, isoform 3 support a less rapid mode of stimulated endocytosis. Accordingly, proximity ligation assay confirmed that dynamin 1 and 2 colocalize with amphiphysin 1 in CGNs, and the latter copurified with both dynamins from cell extracts. In contrast, LDCV-releasing TGNs preferentially employ dynamins 2 and 3 and amphiphysin 1 for evoked endocytosis and lack the fast phase. Hence, stimulation recruits dynamin, clathrin, AP2, and amphiphysin to augment BoNT internalization, and neurons match endocytosis mediators to the different demands for locally recycling SCSVs or replenishing distally synthesized LDCVs.
[Mh] Termos MeSH primário: Toxinas Botulínicas/metabolismo
Endocitose
Neurônios/metabolismo
Neurotoxinas/metabolismo
[Mh] Termos MeSH secundário: Complexo 2 de Proteínas Adaptadoras/genética
Complexo 2 de Proteínas Adaptadoras/metabolismo
Subunidades alfa do Complexo de Proteínas Adaptadoras/genética
Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo
Animais
Toxinas Botulínicas/genética
Toxinas Botulínicas Tipo A
Células Cultivadas
Clatrina/genética
Clatrina/metabolismo
Dinaminas/genética
Dinaminas/metabolismo
Ácido Glutâmico/metabolismo
Camundongos
Camundongos da Linhagem 129
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Transgênicos
Microscopia Confocal
Mutação
Proteínas do Tecido Nervoso/genética
Proteínas do Tecido Nervoso/metabolismo
Neurônios/citologia
Neurotoxinas/genética
Peptídeos/metabolismo
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Interferência de RNA
Ratos
Ratos Sprague-Dawley
Vesículas Secretórias/metabolismo
Vesículas Sinápticas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Protein Complex 2); 0 (Adaptor Protein Complex alpha Subunits); 0 (Clathrin); 0 (Nerve Tissue Proteins); 0 (Neurotoxins); 0 (Peptides); 0 (Protein Isoforms); 0 (adaptor protein complex 2, alpha 2 subunit); 0Y70779M1F (rimabotulinumtoxinB); 147954-52-7 (amphiphysin); 3KX376GY7L (Glutamic Acid); EC 3.4.24.69 (Botulinum Toxins); EC 3.4.24.69 (Botulinum Toxins, Type A); EC 3.6.5.5 (Dynamins)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130504
[St] Status:MEDLINE
[do] DOI:10.1096/fj.13-228973



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