The Experts below are selected from a list of 2889 Experts worldwide ranked by ideXlab platform
Shigeo Ohno - One of the best experts on this subject based on the ideXlab platform.
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the Epithelial circumferential actin belt regulates yap taz through nucleocytoplasmic shuttling of merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
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The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
Kana T. Furukawa - One of the best experts on this subject based on the ideXlab platform.
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the Epithelial circumferential actin belt regulates yap taz through nucleocytoplasmic shuttling of merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
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The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
Kazunari Yamashita - One of the best experts on this subject based on the ideXlab platform.
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the Epithelial circumferential actin belt regulates yap taz through nucleocytoplasmic shuttling of merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
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The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
Natsuki Sakurai - One of the best experts on this subject based on the ideXlab platform.
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the Epithelial circumferential actin belt regulates yap taz through nucleocytoplasmic shuttling of merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
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The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin
Cell Reports, 2017Co-Authors: Kana T. Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo OhnoAbstract:Circumferential actin belts underlying the adherens junctions of Columnar Epithelial Cell monolayers control interCellular surface tension and Cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified. By manipulating actin tension, we demonstrate that circumferential actin belt tension suppresses YAP/TAZ nuclear localization. This suppression requires Merlin, an F-actin binding protein associated with adherens junctions. Merlin physically interacts with YAP/TAZ, and nuclear export sequences of Merlin are required for suppression. Together, with the observation that the association between E-cadherin and Merlin was diminished by tension in circumferential actin belts, our results suggest that released Merlin undergoes nucleocytoplasmic shutting and mediates export of YAP/TAZ from the nucleus.
Akihiko Ito - One of the best experts on this subject based on the ideXlab platform.
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modest static pressure suppresses Columnar Epithelial Cell growth in association with Cell shape and cytoskeletal modifications
Frontiers in Physiology, 2017Co-Authors: Man Hagiyama, Norikazu Yabuta, Daisuke Okuzaki, Takao Inoue, Yasutoshi Takashima, Ryuichiro Kimura, Akihiko ItoAbstract:Intraluminal pressure elevation can cause degenerative disorders, such as ileus and hydronephrosis, and the threshold is fairly low and constant, 20–30 cm H2O. We previously devised a novel two-chamber culture system subjecting Cells cultured on a semipermeable membrane to increased culture medium height (water pressure up to 60 cm H2O). Here, we sought to determine how a continuous pressure load of ~30 cm H2O affects proliferating Epithelial Cells with special interest in the link with Cell morphology. We cultured several different Cell lines using the low static pressure-loadable two-chamber system, and examined Cell growth, Cell cycle, and Cell morphology. Madin–Darby canine kidney (MDCK) Columnar Epithelial Cells were growth-suppressed in a manner dependent on static water pressure ranging from 2–50 cm H2O, without Cell cycle arrest at any specific phase. Two other types of Columnar Epithelial Cells exhibited similar phenotypes. By contrast, spherical Epithelial and mesenchymal Cells were not growth-suppressed, even at 50 cm H2O. Phalloidin staining revealed that 50 cm H2O pressure load vertically flattened and laterally widened Columnar Epithelial Cells and made actin fiber distribution sparse, without affecting total phalloidin intensity per Cell. When the mucosal protectant irsogladine maleate (100 nM) was added to 50-cm-high culture medium, MDCK Cells were reduced in volume and their doubling time shortened. Cell proliferation and morphology are known to be regulated by the Hippo signaling pathway. A pressure load of 50 cm H2O enhanced serine-127 phosphorylation and cytoplasmic retention of YAP, the major constituent of this pathway, suggesting that Hippo pathway was involved in the pressure-induced Cell growth suppression. RNA sequencing of MDCK Cells showed that a 50 cm H2O pressure load upregulated keratin 14, an intermediate filament, 12-fold. This upregulation was confirmed at the protein level by immunofluorescence, suggesting a role in cytoskeletal reinforcement. These results provide evidence that Cell morphology and the cytoskeleton are closely linked to Cell growth. Pathological intraluminal pressure elevation may cause mucosal degeneration by acting directly on this linkage and the Hippo pathway.
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modest static pressure suppresses Columnar Epithelial Cell proliferation in association with Cell shape and cytoskeletal modifications
bioRxiv, 2017Co-Authors: Man Hagiyama, Norikazu Yabuta, Daisuke Okuzaki, Takao Inoue, Yasutoshi Takashima, Ryuichiro Kimura, Akihiko ItoAbstract:Intraluminal pressure elevation can cause degenerative disorders, such as ileus and hydronephrosis, and the threshold is fairly low and constant, 20−30 cm H2O. We previously devised a novel two−chamber culture system subjecting Cells cultured on a semipermeable membrane to increased culture medium height (water pressure up to 60 cm H2O). Here, we cultured several different Cell lines using the low static pressure−loadable two−chamber system, and examined Cell growth, Cell cycle, and Cell morphology. Madin−Darby canine kidney (MDCK) Columnar Epithelial Cells were growth−suppressed in a manner dependent on static water pressure ranging from 2−50 cm H2O, without Cell cycle arrest at any specific phase. Two other types of Columnar Epithelial Cells exhibited similar phenotypes. By contrast, spherical Epithelial and mesenchymal Cells were not growth−suppressed, even at 50 cm H2O. Phalloidin staining revealed that 50 cm H2O pressure load vertically flattened and laterally widened Columnar Epithelial Cells and made actin fiber distribution sparse, without affecting total phalloidin intensity per Cell. When the mucosal protectant irsogladine maleate (100 nM) was added to 50−cm−high culture medium, MDCK Cells were reduced in volume and their doubling time shortened. Cell proliferation and morphology are known to be regulated by the Hippo signaling pathway, but a pressure load of 50 cm H2O did not alter the expression levels of Hippo signaling molecules in Columnar Epithelial Cells, suggesting that this pathway was not involved in the pressure−induced phenotypes. RNA sequencing of MDCK Cells showed that a 50 cm H2O pressure load upregulated keratin 14, an intermediate filament, 12−fold. This upregulation was confirmed at the protein level by immunofluorescence, suggesting a role in cytoskeletal reinforcement. These results provide evidence that Cell morphology and the cytoskeleton are closely linked to Cell growth. Pathological intraluminal pressure elevation may cause mucosal degeneration by acting directly on this linkage.