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[PMID]:28460436
[Au] Autor:Wang W; Jia WD; Hu B; Pan YY
[Ad] Endereço:Department of Medical Oncology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, PR China.
[Ti] Título:RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma.
[So] Source:Oncotarget;8(16):26434-26447, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here we report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro. In addition, RAB10 knockdown suppressed HCC growth in nude mice. Moreover, RAB10 silencing decreased the phosphorylation of InsR, Met/HGFR, Ron/MST1R, Ret, c-Kit/SCFR, EphA3, EphB4, Tyro3/Dtk, Axl, Tie2/TEK, VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly. These results suggest that RAB10 regulates cell survival and proliferation through multiple oncogenic, cell stress and apoptosis pathways. More importantly, high RAB10 expression levels in HCC cells correlated with a poor prognosis in HCC patients. Therefore, our findings revealed an oncogenic role for RAB10 in the pathogenesis of HCC and that RAB10 is a potential molecular target or a biomarker for HCC.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/mortalidade
Expressão Gênica
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/mortalidade
Proteínas rab de Ligação ao GTP/genética
[Mh] Termos MeSH secundário: Animais
Apoptose/genética
Carcinoma Hepatocelular/metabolismo
Carcinoma Hepatocelular/patologia
Pontos de Checagem do Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular
Sobrevivência Celular
Modelos Animais de Doenças
Feminino
Perfilação da Expressão Gênica
Técnicas de Silenciamento de Genes
Xenoenxertos
Seres Humanos
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Masculino
Camundongos
Gradação de Tumores
Estadiamento de Neoplasias
Oncogenes
Prognóstico
Interferência de RNA
Transdução de Sinais
Estresse Fisiológico
Proteínas rab de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.1.- (Rab10 protein, human); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1803
[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
[do] DOI:10.18632/oncotarget.15507


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[PMID]:29281629
[Au] Autor:Ojeda Naharros I; Gesemann M; Mateos JM; Barmettler G; Forbes A; Ziegler U; Neuhauss SCF; Bachmann-Gagescu R
[Ad] Endereço:Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
[Ti] Título:Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors.
[So] Source:PLoS Genet;13(12):e1007150, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane.
[Mh] Termos MeSH primário: Proteínas de Transporte Vesicular/genética
Proteínas de Transporte Vesicular/metabolismo
Proteínas de Peixe-Zebra/genética
Proteínas de Peixe-Zebra/metabolismo
Proteínas rab de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Transporte Biológico
Movimento Celular
Cílios/genética
Cílios/metabolismo
Seres Humanos
Membranas/metabolismo
Opsinas/genética
Opsinas/metabolismo
Células Fotorreceptoras de Vertebrados/metabolismo
Transporte Proteico
Peixe-Zebra
Proteínas rab de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CC2D2A protein, zebrafish); 0 (Opsins); 0 (Vesicular Transport Proteins); 0 (Zebrafish Proteins); EC 3.6.1.- (Rab8a protein, zebrafish); EC 3.6.1.-. (RAB8A protein, human); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007150


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[PMID]:28465352
[Au] Autor:Zhang J; Johnson JL; He J; Napolitano G; Ramadass M; Rocca C; Kiosses WB; Bucci C; Xin Q; Gavathiotis E; Cuervo AM; Cherqui S; Catz SD
[Ad] Endereço:From the Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California 92037.
[Ti] Título:Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A.
[So] Source:J Biol Chem;292(25):10328-10346, 2017 06 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The lysosomal storage disease cystinosis, caused by cystinosin deficiency, is characterized by cell malfunction, tissue failure, and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Here, we show CMA substrate accumulation in cystinotic kidney proximal tubule cells. We also found mislocalization of the CMA lysosomal receptor LAMP2A and impaired substrate translocation into the lysosome caused by defective CMA in cystinosis. The impaired LAMP2A trafficking and localization were rescued either by the expression of wild-type cystinosin or by the disease-associated point mutant CTNS-K280R, which has no cystine transporter activity. Defective LAMP2A trafficking in cystinosis was found to associate with decreased expression of the small GTPase Rab11 and the Rab7 effector RILP. Defective Rab11 trafficking in cystinosis was rescued by treatment with small-molecule CMA activators. RILP expression was restored by up-regulation of the transcription factor EB (TFEB), which was down-regulated in cystinosis. Although LAMP2A expression is independent of TFEB, TFEB up-regulation corrected lysosome distribution and lysosomal LAMP2A localization in cells but not Rab11 defects. The up-regulation of Rab11, Rab7, or RILP, but not its truncated form RILP-C33, rescued LAMP2A-defective trafficking in cystinosis, whereas dominant-negative Rab11 or Rab7 impaired LAMP2A trafficking. Treatment of cystinotic cells with a CMA activator increased LAMP2A localization at the lysosome and increased cell survival. Altogether, we show that LAMP2A trafficking is regulated by cystinosin, Rab11, and RILP and that CMA up-regulation is a potential clinically relevant mechanism to increase cell survival in cystinosis.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Sistemas de Transporte de Aminoácidos Neutros/metabolismo
Cistinose/metabolismo
Proteína 2 de Membrana Associada ao Lisossomo/metabolismo
Lisossomos/metabolismo
Proteínas rab de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Substituição de Aminoácidos
Sistemas de Transporte de Aminoácidos Neutros/genética
Animais
Cistinose/genética
Cistinose/patologia
Ativadores de Enzimas/farmacologia
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Regulação Enzimológica da Expressão Gênica/genética
Proteína 2 de Membrana Associada ao Lisossomo/genética
Lisossomos/genética
Camundongos
Camundongos Knockout
Mutação Puntual
Transporte Proteico/genética
Proteínas rab de Ligação ao GTP/biossíntese
Proteínas rab de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Amino Acid Transport Systems, Neutral); 0 (Enzyme Activators); 0 (Lysosomal-Associated Membrane Protein 2); 0 (Rilp protein, mouse); 0 (cystinosin protein, mouse); 152989-05-4 (rab7 protein); EC 3.6.1.- (rab11 protein); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.764076


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[PMID]:29298974
[Au] Autor:Wachtel R; Bräuning B; Mader SL; Ecker F; Kaila VRI; Groll M; Itzen A
[Ad] Endereço:Center for Integrated Protein Science Munich (CIPSM), Department Chemistry, Technical University of Munich, Lichtenbergstrasse 4, 85747, Garching, Germany.
[Ti] Título:The protease GtgE from Salmonella exclusively targets inactive Rab GTPases.
[So] Source:Nat Commun;9(1):44, 2018 01 03.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Salmonella infections require the delivery of bacterial effectors into the host cell that alter the regulation of host defense mechanisms. The secreted cysteine protease GtgE from S. Typhimurium manipulates vesicular trafficking by modifying the Rab32 subfamily via cleaving the regulatory switch I region. Here we present a comprehensive biochemical, structural, and computational characterization of GtgE in complex with Rab32. Interestingly, GtgE solely processes the inactive GDP-bound GTPase. The crystal structure of the Rab32:GDP substrate in complex with the inactive mutant GtgE reveals the molecular basis of substrate recognition. In combination with atomistic molecular dynamics simulations, the structural determinants for protein and activity-state specificity are identified. Mutations in a central interaction hub lead to loss of the strict GDP specificity. Our findings shed light on the sequence of host cell manipulation events during Salmonella infection and provide an explanation for the dependence on the co-secreted GTPase activating protein SopD2.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Cisteína Proteases/metabolismo
Salmonella enterica/enzimologia
Proteínas rab de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Simulação de Dinâmica Molecular
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (SopD protein, Salmonella); EC 3.4.- (Cysteine Proteases); EC 3.6.1.- (Rab32 protein, human); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02110-1


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[PMID]:29191386
[Au] Autor:Xue H; Tian GY
[Ad] Endereço:Department of Pathology, Jinhua People's Hospital, Jinhua City, Zhejiang Province, 321000, China.
[Ti] Título:MiR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23.
[So] Source:Arch Biochem Biophys;637:48-55, 2018 01 01.
[Is] ISSN:1096-0384
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulating documents have revealed that microRNAs (miRNAs) play critical roles in the development and progression of tumors. MiR-429 has been reported to be involved in regulating various cellular processes. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) still need to be further studied. The present study aimed to investigate the function of miR-429 in the progression of HCC. In terms of this paper, it was found that miR-429 was down-regulated in HCC tissues and cells. After being transfected with miR-429 mimics, miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429. Rescue assays further verified that the function of miR-429 in HCC cells was exerted through targeting RAB23. In general, it was concluded that the signal pathway miR-429/RAB23 might be a potential target for HCC treatment.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/genética
Neoplasias Hepáticas/genética
MicroRNAs/genética
Proteínas rab de Ligação ao GTP/genética
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/patologia
Carcinoma Hepatocelular/secundário
Linhagem Celular Tumoral
Movimento Celular
Regulação para Baixo
Transição Epitelial-Mesenquimal/genética
Regulação Neoplásica da Expressão Gênica
Células Hep G2
Seres Humanos
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
MicroRNAs/metabolismo
Mimetismo Molecular
Transdução de Sinais
Transfecção
Regulação para Cima
Proteínas rab de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (MIRN429 microRNA, human); 0 (MicroRNAs); EC 3.6.1.- (RAB23 protein, human); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE


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[PMID]:28455410
[Au] Autor:Caplan S
[Ad] Endereço:From the Department of Biochemistry and Molecular Biology and The Fred and Pamela Buffett Cancer Center, The University of Nebraska Medical Center, Omaha, Nebraska 68198-5870 scaplan@unmc.edu.
[Ti] Título:Into the linker's DENN: A tyrosine's control of autophagy.
[So] Source:J Biol Chem;292(17):7283-7284, 2017 04 28.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The small GTP-binding protein Rab12 plays an important role in the initiation of starvation-induced macroautophagy (autophagy) and is activated by the guanine-nucleotide exchange factor DENND3. However, the molecular mechanism by which DENND3 becomes activated has remained elusive. Xu and McPherson now identify a novel mechanism of DENND3 intramolecular binding that is regulated by the phosphorylation of a single tyrosine residue.
[Mh] Termos MeSH primário: Autofagia
Tirosina
[Mh] Termos MeSH secundário: Fatores de Troca do Nucleotídeo Guanina/química
Fosforilação
Proteínas rab de Ligação ao GTP/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; COMMENT
[Nm] Nome de substância:
0 (Guanine Nucleotide Exchange Factors); 42HK56048U (Tyrosine); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.H116.772434


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[PMID]:28945820
[Au] Autor:Guichard A; Jain P; Moayeri M; Schwartz R; Chin S; Zhu L; Cruz-Moreno B; Liu JZ; Aguilar B; Hollands A; Leppla SH; Nizet V; Bier E
[Ad] Endereço:Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, United States of America.
[Ti] Título:Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport.
[So] Source:PLoS Pathog;13(9):e1006603, 2017 Sep.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.
[Mh] Termos MeSH primário: Antígenos de Bactérias/farmacologia
Toxinas Bacterianas/farmacologia
Edema/metabolismo
Endossomos/efeitos dos fármacos
Junções Intercelulares/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fatores de Ribosilação do ADP/metabolismo
Adenilil Ciclases/metabolismo
Animais
Caderinas/metabolismo
Linhagem Celular
Endossomos/metabolismo
Junções Intercelulares/metabolismo
Transporte Proteico/efeitos dos fármacos
Proteínas rab de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Bacterial Toxins); 0 (Cadherins); 0 (anthrax toxin); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ADP-ribosylation factor 6); EC 3.6.5.2 (rab GTP-Binding Proteins); EC 4.6.1.1 (Adenylyl Cyclases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006603


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[PMID]:28934205
[Au] Autor:Zhou F; Zou S; Chen Y; Lipatova Z; Sun D; Zhu X; Li R; Wu Z; You W; Cong X; Zhou Y; Xie Z; Gyurkovska V; Liu Y; Li Q; Li W; Cheng J; Liang Y; Segev N
[Ad] Endereço:College of Life Sciences, Key Laboratory of Agricultural Environmental Microbiology of Ministry of Agriculture, Nanjing Agricultural University, Nanjing, China.
[Ti] Título:A Rab5 GTPase module is important for autophagosome closure.
[So] Source:PLoS Genet;13(9):e1007020, 2017 Sep.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation. Fusion of APs and endosomes with the vacuole (the yeast lysosome) requires the Ypt7 GTPase module. We have previously shown that the Rab5-related Vps21, within its endocytic GTPase module, regulates autophagy. However, it was not clear which autophagy step it regulates. Here, we show that this module, which includes the Vps9 activator, the Rab5-related Vps21, the CORVET tethering complex, and the Pep12 SNARE, functions after AP expansion and before AP closure. Whereas APs are not formed in mutant cells depleted for Atgs, sealed APs accumulate in cells depleted for the Ypt7 GTPase module members. Importantly, depletion of individual members of the Vps21 module results in a novel phenotype: accumulation of unsealed APs. In addition, we show that Vps21-regulated AP closure precedes another AP maturation step, the previously reported PI3P phosphatase-dependent Atg dissociation. Our results delineate three successive steps in the autophagy pathway regulated by Rabs, Ypt1, Vps21 and Ypt7, and provide the first insight into the upstream regulation of AP closure.
[Mh] Termos MeSH primário: Autofagossomos/metabolismo
Endocitose/genética
Transporte Proteico/genética
Proteínas rab de Ligação ao GTP/genética
Proteínas rab5 de Ligação ao GTP/genética
[Mh] Termos MeSH secundário: Autofagia/genética
Proteínas Relacionadas à Autofagia/genética
Endossomos/genética
Lisossomos/genética
Fosfatidilinositol 3-Quinases/genética
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
Vacúolos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autophagy-Related Proteins); 0 (Saccharomyces cerevisiae Proteins); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.6.1.- (VPS21 protein, S cerevisiae); EC 3.6.1.- (YPT1 protein, S cerevisiae); EC 3.6.1.- (YPT7 protein, S cerevisiae); EC 3.6.5.2 (rab GTP-Binding Proteins); EC 3.6.5.2 (rab5 GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007020


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[PMID]:28928133
[Au] Autor:Casanova JE; Winckler B
[Ad] Endereço:Department of Cell Biology, University of Virginia, Charlottesville, VA.
[Ti] Título:A new Rab7 effector controls phosphoinositide conversion in endosome maturation.
[So] Source:J Cell Biol;216(10):2995-2997, 2017 Oct 02.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endosome maturation requires a coordinated change in the Rab GTPase and phosphoinositide composition of the endosomal membrane. In this issue, Liu et al. (2017. https://doi.org/10.1083/jcb.201705151) identify WDR91 as a ubiquitous Rab7 effector that inhibits phosphatidylinositol 3-kinase activity on endosomes and is critical for endosome maturation, viability, and dendrite growth of neurons in vivo.
[Mh] Termos MeSH primário: Endossomos
Proteínas rab de Ligação ao GTP
[Mh] Termos MeSH secundário: Fosfatidilinositol 3-Quinases
Fosfatidilinositóis
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphatidylinositols); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201709034


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[PMID]:28922401
[Au] Autor:Taglauer ES; Artemiuk PA; Hanscom SR; Lindsay AJ; Wuebbolt D; Breathnach FM; Tully EC; Khan AR; McCaffrey MW
[Ad] Endereço:Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
[Ti] Título:Rab11 family expression in the human placenta: Localization at the maternal-fetal interface.
[So] Source:PLoS One;12(9):e0184864, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human placenta, with novel localization at the maternal-fetal interface.
[Mh] Termos MeSH primário: Regulação Enzimológica da Expressão Gênica/fisiologia
Placenta/enzimologia
Proteínas da Gravidez/biossíntese
Proteínas rab de Ligação ao GTP/biossíntese
[Mh] Termos MeSH secundário: Adulto
Feminino
Células HeLa
Seres Humanos
Imuno-Histoquímica
Gravidez
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pregnancy Proteins); 0 (Rab25 protein, human); EC 3.6.1.- (Rab14 protein, human); EC 3.6.1.- (rab11 protein); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184864



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