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Pesquisa : A11.284.180.700 [Categoria DeCS]
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  1 / 3661 MEDLINE  
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[PMID]:29244882
[Au] Autor:Meissner JM; Sikorski AF; Nawara T; Grzesiak J; Marycz K; Boguslawska DM; Michalczyk I; Lecomte MC; Machnicka B
[Ad] Endereço:Laboratory of Cytobiochemistry, Biotechnology Faculty, University of Wroclaw, Wroclaw, Poland.
[Ti] Título:αII-spectrin in T cells is involved in the regulation of cell-cell contact leading to immunological synapse formation?
[So] Source:PLoS One;12(12):e0189545, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:T-lymphocyte activation after antigen presentation to the T-Cell Receptor (TCR) is a critical step in the development of proper immune responses to infection and inflammation. This dynamic process involves reorganization of the actin cytoskeleton and signaling molecules at the cell membrane, leading to the formation of the Immunological Synapse (IS). The mechanisms regulating the formation of the IS are not completely understood. Nonerythroid spectrin is a membrane skeletal protein involved in the regulation of many cellular processes, including cell adhesion, signaling and actin cytoskeleton remodeling. However, the role of spectrin in IS formation has not been explored. We used molecular, imaging and cellular approaches to show that nonerythroid αII-spectrin redistributes to the IS during T-cell activation. The redistribution of spectrin coincides with the relocation of CD45 and LFA-1, two components essential for IS formation and stability. We assessed the role of spectrin by shRNA-mediated depletion from Jurkat T cells and show that spectrin-depleted cells exhibit decreased adhesion and are defective in forming lamellipodia and filopodia. Importantly, IS formation is impaired in spectrin-depleted cells. Thus, spectrin may be engaged in regulation of distinct events necessary for the establishment and maturity of the IS: besides the involvement of spectrin in the control of CD45 and LFA-1 surface display, spectrin acts in the establishment of cell-cell contact and adhesion processes during the formation of the IS.
[Mh] Termos MeSH primário: Sinapses Imunológicas/fisiologia
Espectrina/fisiologia
[Mh] Termos MeSH secundário: Adesão Celular
Seres Humanos
Células Jurkat
Transporte Proteico
Pseudópodes/metabolismo
Pseudópodes/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
12634-43-4 (Spectrin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189545


  2 / 3661 MEDLINE  
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[PMID]:29240845
[Au] Autor:Reimer M; Denby E; Zustiak SP; Schober JM
[Ad] Endereço:Department of Pharmaceutical Sciences, Southern Illinois University Edwardsville, Edwardsville, Illinois, United States of America.
[Ti] Título:Ras GAP-related and C-terminal domain-dependent localization and tumorigenic activities of IQGAP1 in melanoma cells.
[So] Source:PLoS One;12(12):e0189589, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IQGAP1 interacts with a number of binding partners through a calponin homology domain (CHD), a WW motif, IQ repeats, a Ras GAP-related domain (GRD), and a conserved C-terminal (CT) domain. Among various biological and cellular functions, IQGAP1 is known to play a role in actin cytoskeleton dynamics during membrane ruffling and lamellipodium protrusion. In addition, phosphorylation near the CT domain is thought to control IQGAP1 activity through regulation of intramolecular interaction. In a previous study, we discovered that IQGAP1 preferentially localizes to retracting areas in B16F10 mouse melanoma cells, not areas of membrane ruffling and lamellipodium protrusion. Nothing is known of the domains needed for retraction localization and very little is known of IQGAP1 function in the actin cytoskeleton of melanoma cells. Thus, we examined localization of IQGAP1 mutants to retracting areas, and characterized knock down phenotypes on tissue culture plastic and physiologic-stiffness hydrogels. Localization of IQGAP1 mutants (S1441E/S1443D, S1441A/S1443A, ΔCHD, ΔGRD or ΔCT) to retracting and protruding cell edges were measured. In retracting areas there was a decrease in S1441A/S1443A, ΔGRD and ΔCT localization, a minor decrease in ΔCHD localization, and normal localization of the S1441E/S1443D mutant. In areas of cell protrusion just behind the lamellipodium leading edge, we surprisingly observed both ΔGRD and ΔCT localization, and increased number of microtubules. IQGAP1 knock down caused loss of cell polarity on laminin-coated glass, decreased proliferation on tissue culture polystyrene, and abnormal spheroid growth on laminin-coated hydrogels. We propose that the GRD and CT domains regulate IQGAP1 localization to retracting actin networks to promote a tumorigenic role in melanoma cells.
[Mh] Termos MeSH primário: Melanoma Experimental/metabolismo
Proteínas Ativadoras de ras GTPase/metabolismo
[Mh] Termos MeSH secundário: Citoesqueleto de Actina/metabolismo
Animais
Carcinogênese
Linhagem Celular Tumoral
Técnicas de Silenciamento de Genes
Hidrogéis
Melanoma Experimental/patologia
Camundongos
Microtúbulos/metabolismo
Mutação
Pseudópodes/metabolismo
Proteínas Ativadoras de ras GTPase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydrogels); 0 (IQ motif containing GTPase activating protein 1); 0 (ras GTPase-Activating Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189589


  3 / 3661 MEDLINE  
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[PMID]:28455372
[Au] Autor:Mallik B; Dwivedi MK; Mushtaq Z; Kumari M; Verma PK; Kumar V
[Ad] Endereço:Department of Biological Sciences, AB-3, Indian Institute of Science Education and Research, Bhauri, Bhopal, Madhya Pradesh 462066, India.
[Ti] Título:Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in .
[So] Source:Development;144(11):2032-2044, 2017 06 01.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of BAR-domain proteins and identified islet cell autoantigen 69 kDa (ICA69) as one of the key regulators of morphological differentiation of the larval neuromuscular junction (NMJ). We show that ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of ICA69 deforms liposomes Full-length ICA69 and the ICAC but not the N-BAR domain of ICA69 induce filopodia in cultured cells. Consistent with its cytoskeleton regulatory role, mutants show reduced α-Spectrin immunoreactivity at the larval NMJ. Manipulating levels of ICA69 or its interactor PICK1 alters the synaptic level of ionotropic glutamate receptors (iGluRs). Moreover, reducing PICK1 or Rab2 levels phenocopies mutation. Interestingly, Rab2 regulates not only synaptic iGluR but also ICA69 levels. Thus, our data suggest that: (1) ICA69 regulates NMJ organization through a pathway that involves PICK1 and Rab2, and (2) Rab2 functions genetically upstream of ICA69 and regulates NMJ organization and targeting/retention of iGluRs by regulating ICA69 levels.
[Mh] Termos MeSH primário: Autoantígenos/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/metabolismo
Junção Neuromuscular/metabolismo
Proteína rab2 de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Técnicas de Silenciamento de Genes
Larva/metabolismo
Lipossomos
Mutação/genética
Subunidades Proteicas/metabolismo
Transporte Proteico
Pseudópodes/metabolismo
Interferência de RNA
Receptores Ionotrópicos de Glutamato/metabolismo
Sinapses/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Autoantigens); 0 (Drosophila Proteins); 0 (Liposomes); 0 (Protein Subunits); 0 (Receptors, Ionotropic Glutamate); EC 3.6.5.2 (rab2 GTP-Binding Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1242/dev.145920


  4 / 3661 MEDLINE  
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[PMID]:29049733
[Au] Autor:Keller KE; Bradley JM; Sun YY; Yang YF; Acott TS
[Ad] Endereço:Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
[Ti] Título:Tunneling Nanotubes are Novel Cellular Structures That Communicate Signals Between Trabecular Meshwork Cells.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5298-5307, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: The actin cytoskeleton of trabecular meshwork (TM) cells plays a role in regulating aqueous humor outflow. Many studies have investigated stress fibers, but F-actin also assembles into other supramolecular structures including filopodia. Recently, specialized filopodia called tunneling nanotubes (TNTs) have been described, which communicate molecular signals and organelles directly between cells. Here, we investigate TNT formation by TM cells. Methods: Human TM cells were labeled separately with the fluorescent dyes, DiO and DiD, or with mitochondrial dye. Fixed or live TM cells were imaged using confocal microscopy. Image analysis software was used to track fluorescent vesicles and count the number and length of filopodia. The number of fluorescently labeled vesicles transferred between cells was counted in response to specific inhibitors of the actin cytoskeleton. Human TM tissue was stained with phalloidin. Results: Live-cell confocal imaging of cultured TM cells showed transfer of fluorescently labeled vesicles and mitochondria via TNTs. In TM tissue, a long (160 µm) actin-rich cell process bridged an intertrabecular space and did not adhere to the substratum. Treatment of TM cells with CK-666, an Arp2/3 inhibitor, significantly decreased the number and length of filopodia, decreased transfer of fluorescently labeled vesicles and induced thick stress fibers compared to vehicle control. Conversely, inhibiting stress fibers using Y27632 increased transfer of vesicles and induced long cell processes. Conclusions: Identification of TNTs provides a means by which TM cells can directly communicate with each other over long distances. This may be particularly important to overcome limitations of diffusion-based signaling in the aqueous humor fluid environment.
[Mh] Termos MeSH primário: Comunicação Celular/fisiologia
Nanotubos
Pseudópodes/fisiologia
Transdução de Sinais/fisiologia
Malha Trabecular/citologia
Vesículas Transportadoras/fisiologia
[Mh] Termos MeSH secundário: Complexo 2-3 de Proteínas Relacionadas à Actina/antagonistas & inibidores
Actinas/antagonistas & inibidores
Actinas/metabolismo
Adolescente
Adulto
Amidas/farmacologia
Criança
Pré-Escolar
Inibidores Enzimáticos/farmacologia
Corantes Fluorescentes/metabolismo
Seres Humanos
Indóis/farmacologia
Microscopia Confocal
Meia-Idade
Piridinas/farmacologia
Coloração e Rotulagem
Malha Trabecular/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actin-Related Protein 2-3 Complex); 0 (Actins); 0 (Amides); 0 (CK-0944666); 0 (Enzyme Inhibitors); 0 (Fluorescent Dyes); 0 (Indoles); 0 (Pyridines); 138381-45-0 (Y 27632)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-22732


  5 / 3661 MEDLINE  
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[PMID]:28947178
[Au] Autor:Talebian A; Britton R; Ammanuel S; Bepari A; Sprouse F; Birnbaum SG; Szabó G; Tamamaki N; Gibson J; Henkemeyer M
[Ad] Endereço:Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
[Ti] Título:Autonomous and non-autonomous roles for ephrin-B in interneuron migration.
[So] Source:Dev Biol;431(2):179-193, 2017 11 15.
[Is] ISSN:1095-564X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:While several studies indicate the importance of ephrin-B/EphB bidirectional signaling in excitatory neurons, potential roles for these molecules in inhibitory neurons are largely unknown. We identify here an autonomous receptor-like role for ephrin-B reverse signaling in the tangential migration of interneurons into the neocortex using ephrin-B (EfnB1/B2/B3) conditional triple mutant (TM ) mice and a forebrain inhibitory neuron specific Cre driver. Inhibitory neuron deletion of the three EfnB genes leads to reduced interneuron migration, abnormal cortical excitability, and lethal audiogenic seizures. Truncated and intracellular point mutations confirm the importance of ephrin-B reverse signaling in interneuron migration and cortical excitability. A non-autonomous ligand-like role was also identified for ephrin-B2 that is expressed in neocortical radial glial cells and required for proper tangential migration of GAD65-positive interneurons. Our studies thus define both receptor-like and ligand-like roles for the ephrin-B molecules in controlling the migration of interneurons as they populate the neocortex and help establish excitatory/inhibitory (E/I) homeostasis.
[Mh] Termos MeSH primário: Movimento Celular
Efrinas/metabolismo
Interneurônios/citologia
Interneurônios/metabolismo
[Mh] Termos MeSH secundário: Animais
Feminino
Deleção de Genes
Ligantes
Camundongos
Modelos Biológicos
Mutação/genética
Neocórtex/citologia
Neocórtex/metabolismo
Inibição Neural
Prosencéfalo/citologia
Prosencéfalo/metabolismo
Pseudópodes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Ephrins); 0 (Ligands)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE


  6 / 3661 MEDLINE  
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[PMID]:28898677
[Au] Autor:Arata M; Sugimura K; Uemura T
[Ad] Endereço:Graduate School of Biostudies, Kyoto University, South Campus Research Building (Building G), Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
[Ti] Título:Difference in Dachsous Levels between Migrating Cells Coordinates the Direction of Collective Cell Migration.
[So] Source:Dev Cell;42(5):479-497.e10, 2017 Sep 11.
[Is] ISSN:1878-1551
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In contrast to extracellular chemotactic gradients, how cell-adhesion molecules contribute to directing cell migration remains more elusive. Here we studied the collective migration of Drosophila larval epidermal cells (LECs) along the anterior-posterior axis and propose a migrating cell group-autonomous mechanism in which an atypical cadherin Dachsous (Ds) plays a pivotal role. In each abdominal segment, the amount of Ds in each LEC varied along the axis of migration (Ds imbalance), which polarized Ds localization at cell boundaries. This Ds polarity was necessary for coordinating the migratory direction. Another atypical cadherin, Fat (Ft), and an unconventional myosin Dachs, both of which bind to Ds, also showed biased cell-boundary localizations, and both were required for the migration. Altogether, we propose that the Ds imbalance within the migrating tissue provides the directional cue and that this is decoded by Ds-Ft-mediated cell-cell contacts, which restricts lamellipodia formation to the posterior end of the cell.
[Mh] Termos MeSH primário: Caderinas/metabolismo
Movimento Celular
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/citologia
Drosophila melanogaster/metabolismo
[Mh] Termos MeSH secundário: Abdome/crescimento & desenvolvimento
Animais
Apoptose
Padronização Corporal
Polaridade Celular
Forma Celular
Epiderme/citologia
Epiderme/metabolismo
Técnicas de Silenciamento de Genes
Imagem Tridimensional
Larva/citologia
Pseudópodes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cadherins); 0 (Drosophila Proteins); 0 (dachsous protein, Drosophila)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE


  7 / 3661 MEDLINE  
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[PMID]:28870903
[Au] Autor:Uehara S; Saito K; Asami H; Ohta Y
[Ad] Endereço:Division of Cell Biology, Department of Biosciences, School of Science, Kitasato University, Kanagawa, Japan.
[Ti] Título:Role of ARHGAP24 in ADP Ribosylation Factor 6 (ARF6)-dependent Pseudopod Formation in Human Breast Carcinoma Cells.
[So] Source:Anticancer Res;37(9):4837-4844, 2017 09.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: The small GTPase ADP ribosylation factor 6 (ARF6) promotes carcinoma cell invasion and metastasis through remodeling of actin cytoskeleton and formation of pseudopod that is regulated by RAC. RHO GTPase activating protein 24 (ARHGAP24), a RAC-specific GTPase activating protein, binds to activated ARF6 and is recruited to the plasma membrane. The aim of the present study was to demonstrate if ARHGAP24 is involved in the ARF6-mediated formation of pseudopods in breast carcinoma cells. MATERIALS AND METHODS: The formation of pseudopods induced by activated ARF6 was monitored using MDA-MB-231 human breast carcinoma cells. The effect of knockdown of endogenous ARHGAP24 by siRNA was examined. RESULTS: Knockdown of ARHGAP24 in MDA-MB-231 carcinoma cells increased the lifespan of pseudopods to retract, which resulted in increased length of pseudopods induced by activated ARF6. ARHGAP24 required a binding site of ARF6 to achieve ARF6-dependent actin remodeling. CONCLUSION: ARHGAP24 may regulate pseudopod formation downstream of activated ARF6 in MDA-MB-231 human breast carcinoma cells.
[Mh] Termos MeSH primário: Fatores de Ribosilação do ADP/metabolismo
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Proteínas Ativadoras de GTPase/metabolismo
Pseudópodes/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Forma Celular
Matriz Extracelular/metabolismo
Feminino
Proteínas Ativadoras de GTPase/química
Técnicas de Silenciamento de Genes
Células HEK293
Seres Humanos
Ligação Proteica
Domínios Proteicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARHGAP24 protein, human); 0 (GTPase-Activating Proteins); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ADP-ribosylation factor 6)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE


  8 / 3661 MEDLINE  
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[PMID]:28867286
[Au] Autor:Mueller J; Szep G; Nemethova M; de Vries I; Lieber AD; Winkler C; Kruse K; Small JV; Schmeiser C; Keren K; Hauschild R; Sixt M
[Ad] Endereço:Institute of Science and Technology Austria (IST Austria), am Campus 1, 3400 Klosterneuburg, Austria.
[Ti] Título:Load Adaptation of Lamellipodial Actin Networks.
[So] Source:Cell;171(1):188-200.e16, 2017 Sep 21.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.
[Mh] Termos MeSH primário: Citoesqueleto de Actina/química
Citoesqueleto de Actina/ultraestrutura
Queratinócitos/ultraestrutura
Pseudópodes/química
Pseudópodes/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Membrana Celular/química
Queratinócitos/química
Microscopia Eletrônica
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


  9 / 3661 MEDLINE  
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[PMID]:28859089
[Au] Autor:Gujar MR; Stricker AM; Lundquist EA
[Ad] Endereço:Department of Molecular Biosciences, Program in Molecular, Cellular, and Developmental Biology, The University of Kansas, Lawrence, KS, United States of America.
[Ti] Título:Flavin monooxygenases regulate Caenorhabditis elegans axon guidance and growth cone protrusion with UNC-6/Netrin signaling and Rac GTPases.
[So] Source:PLoS Genet;13(8):e1006998, 2017 Aug.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The guidance cue UNC-6/Netrin regulates both attractive and repulsive axon guidance. Our previous work showed that in C. elegans, the attractive UNC-6/Netrin receptor UNC-40/DCC stimulates growth cone protrusion, and that the repulsive receptor, an UNC-5:UNC-40 heterodimer, inhibits growth cone protrusion. We have also shown that inhibition of growth cone protrusion downstream of the UNC-5:UNC-40 repulsive receptor involves Rac GTPases, the Rac GTP exchange factor UNC-73/Trio, and the cytoskeletal regulator UNC-33/CRMP, which mediates Semaphorin-induced growth cone collapse in other systems. The multidomain flavoprotein monooxygenase (FMO) MICAL (Molecule Interacting with CasL) also mediates growth cone collapse in response to Semaphorin by directly oxidizing F-actin, resulting in depolymerization. The C. elegans genome does not encode a multidomain MICAL-like molecule, but does encode five flavin monooxygenases (FMO-1, -2, -3, -4, and 5) and another molecule, EHBP-1, similar to the non-FMO portion of MICAL. Here we show that FMO-1, FMO-4, FMO-5, and EHBP-1 may play a role in UNC-6/Netrin directed repulsive guidance mediated through UNC-40 and UNC-5 receptors. Mutations in fmo-1, fmo-4, fmo-5, and ehbp-1 showed VD/DD axon guidance and branching defects, and variably enhanced unc-40 and unc-5 VD/DD axon guidance defects. Developing growth cones in vivo of fmo-1, fmo-4, fmo-5, and ehbp-1 mutants displayed excessive filopodial protrusion, and transgenic expression of FMO-5 inhibited growth cone protrusion. Mutations suppressed growth cone inhibition caused by activated UNC-40 and UNC-5 signaling, and activated Rac GTPase CED-10 and MIG-2, suggesting that these molecules are required downstream of UNC-6/Netrin receptors and Rac GTPases. From these studies we conclude that FMO-1, FMO-4, FMO-5, and EHBP-1 represent new players downstream of UNC-6/Netrin receptors and Rac GTPases that inhibit growth cone filopodial protrusion in repulsive axon guidance.
[Mh] Termos MeSH primário: Orientação de Axônios/genética
Proteínas de Caenorhabditis elegans/genética
Caenorhabditis elegans/genética
Oxigenases de Função Mista/genética
Proteínas do Tecido Nervoso/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Caenorhabditis elegans/crescimento & desenvolvimento
Dinitrocresóis/metabolismo
Mutação
Netrinas
Pseudópodes/genética
Pseudópodes/metabolismo
Transdução de Sinais
Proteínas rac de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Dinitrocresols); 0 (Nerve Tissue Proteins); 0 (Netrins); 0 (UNC-6 protein, C elegans); 1604ZJR09T (4,6-dinitro-o-cresol); EC 1.- (Mixed Function Oxygenases); EC 3.6.5.2 (rac GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006998


  10 / 3661 MEDLINE  
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[PMID]:28846922
[Au] Autor:Wu CY; Tsai YY; Chen SY; Lin YP; Shin JW; Wu CC; Yang BC
[Ad] Endereço:Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan. Electronic address: jawork520@yahoo.com.tw.
[Ti] Título:Interaction of Zap70 and CXCR4 receptor at lamellipodia that determines the directionality during Jurkat T cells chemotaxis.
[So] Source:Mol Immunol;90:245-254, 2017 Oct.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Directional migration of T-lymphocytes is a key process during immune activation and is tightly regulated both temporally and spatially. The initial cell membrane protrusion at a particular site is critical for determining the direction of cell migration. In this study, we found that ZAP-70 protein appeared not only at the margin of the spreading areas of polarized Jurkat T cells but also formed clusters near the center of the cell body on a fibronectin plate. Specifically, some pZAP-70 was located at the lamellipodia/filopodia and was closely associated with the most extended membrane contact. To visualize the dynamic distribution of ZAP-70 on migrating Jurkat T cells, we generated a fluorescent ZAP-70-EGFP fusion protein (hZAP70G). Expression of the hZAP70G in P116 cells, a ZAP-70 defective Jurkat derivative, restored its chemotactic migration toward SDF-1, adhesion to fibronectin matrix, and integrin activation. In addition, the distribution of hZAP70G protein is associated with changes in cell shape, specifically the membrane protrusion step, forming filopodia/lamellipodia and a retracting uropod. Furthermore, SDF-1 stimulated the formation of ZAP-70 and CXCR4 complex. CXCR4 was observed mainly at the leading edge of migrating cell. The localization of ZAP-70 at the very front edge of protruding lamellipodia was close to CXCR4 and a part of them were overlapped. Collectively, our data describe the critical early step of directional cell movement toward SDF-1 that ZAP-70 is recruited to the CXCR4 at the leading edge of membrane and consequently modulates lamellipodia/filopodia formation and integrin activation.
[Mh] Termos MeSH primário: Quimiocina CXCL12/metabolismo
Quimiotaxia de Leucócito/fisiologia
Pseudópodes/metabolismo
Receptores CXCR4/metabolismo
Proteína-Tirosina Quinase ZAP-70/metabolismo
[Mh] Termos MeSH secundário: Adesão Celular/genética
Linhagem Celular Tumoral
Quimiotaxia de Leucócito/genética
Fibronectinas/metabolismo
Proteínas de Fluorescência Verde/genética
Seres Humanos
Integrinas/metabolismo
Células Jurkat
Ativação Linfocitária/imunologia
Células MCF-7
Transdução de Sinais/imunologia
Linfócitos T/imunologia
Linfócitos T/fisiologia
Proteína-Tirosina Quinase ZAP-70/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CXCL12 protein, human); 0 (CXCR4 protein, human); 0 (Chemokine CXCL12); 0 (Fibronectins); 0 (Integrins); 0 (Receptors, CXCR4); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 2.7.10.2 (ZAP-70 Protein-Tyrosine Kinase); EC 2.7.10.2 (ZAP70 protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE



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