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Yoshimi Takai - One of the best experts on this subject based on the ideXlab platform.
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Dynamic expression of Nectins in enamel organs of mouse incisors
Journal of Oral Biosciences, 2017Co-Authors: Tsubasa Kawashima, Yoshimi Takai, Jiro Takito, Yukie Shimada, Masashi Sato, Mitsuko Inoue, Takashi Miyazaki, Muneaki Miyata, Yoshiyuki Rikitake, Masanori NakamuraAbstract:Abstract Objectives Nectins are immunoglobulin-like cell–cell adhesion molecules and are of four types, namely, Nectin-1, Nectin-2, Nectin-3, and Nectin-4. Cleft lip/palate-ectodermal dysplasia is caused by a mutation in the Nectin-1 gene locus. However, Nectin-1-deficient (KO) mice only show mild tooth defects. This study determined the intracellular localization of Nectins in mouse mandibular incisors to identify their heterophilic interactions during amelogenesis. Methods Nectin localization was determined by performing immunohistochemical analysis with confocal microscopy. Nectin gene expression was determined by performing quantitative reverse transcription-PCR. Phenotypes of Nectin-2 - KO mice were examined by performing micro-computed tomography, histological analysis, and organ culture. Results We found that mRNA levels of Nectin-1 and Nectin-3 genes were higher than those of Nectin-2 and Nectin-4 genes in mouse enamel organs. Nectin-2 and Nectin-4 were strongly expressed at the apical adherens junctions of secretory-stage ameloblasts, whereas Nectin-1 and Nectin-3 were distributed between the basal adherens junction of maturation-stage ameloblasts and the stratum intermedium and papillary layers. Nectin-2-KO mice showed normal mandibular tooth shape, incisor surface pigmentation, and histology. Moreover, organ cultures of the tooth organs of Nectin-2-KO mice proceeded normally. Conclusion These results indicate that Nectins show graded and overlapping distribution in mouse incisors.
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Nectin spot: a novel type of Nectin-mediated cell adhesion apparatus
The Biochemical journal, 2016Co-Authors: Kiyohito Mizutani, Yoshimi TakaiAbstract:Nectins are Ca 2+ -independent immunoglobulin (Ig) superfamily cell adhesion molecules constituting a family with four members, all of which have three Ig-like loops at their extracellular regions. Nectins play roles in the formation of a variety of cell–cell adhesion apparatuses. There are at least three types of Nectin-mediated cell adhesions: afadin- and cadherin-dependent, afadin-dependent and cadherin-independent, and afadin- and cadherin-independent. In addition, Nectins trans -interact with Nectin-like molecules (Necls) with three Ig-like loops and other Ig-like molecules with one to three Ig-like loops. Furthermore, Nectins and Necls cis -interact with membrane receptors and integrins, some of which are associated with the Nectin-mediated cell adhesions, and play roles in the regulation of many cellular functions, such as cell polarization, movement, proliferation, differentiation, and survival, co-operatively with these cell surface proteins. The Nectin-mediated cell adhesions are implicated in a variety of diseases, including genetic disorders, neural disorders, and cancers. Of the three types of Nectin-mediated cell adhesions, the afadin- and cadherin-dependent apparatus has been most extensively investigated, but the examples of the third type of apparatus independent of afadin and cadherin are recently increasing and its morphological and functional properties have been well characterized. We review here recent advances in research on this type of Nectin-mediated cell adhesion apparatus, which is named Nectin spot.
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Regulatory role of the cell adhesion molecule Nectin-1 in GABAergic inhibitory synaptic transmission in the CA3 region of mouse hippocampus.
Genes to cells : devoted to molecular & cellular mechanisms, 2015Co-Authors: Xiaoqi Geng, Akira Mizoguchi, Yoshimi Takai, Takeshi Fujiwara, Tomohiko Maruo, Kenji Mandai, Shujie Wang, Masahiro MoriAbstract:Proper operation of a neural circuit relies on both excitatory and inhibitory synapses. We previously showed that cell adhesion molecules Nectin-1 and Nectin-3 are localized at puncta adherentia junctions of the hippocampal mossy fiber glutamatergic excitatory synapses and that they do not regulate the excitatory synaptic transmission onto the CA3 pyramidal cells. We studied here the roles of these Nectins in the GABAergic inhibitory synaptic transmission onto the CA3 pyramidal cells using Nectin-1-deficient and Nectin-3-deficient cultured mouse hippocampal slices. In these mutant slices, the amplitudes and frequencies of miniature excitatory postsynaptic currents were indistinguishable from those in the control slices. In the Nectin-1-deficient slices, but not in the Nectin-3-deficient slices, however, the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) was larger than that in the control slices, although the frequency of the mIPSCs was not different between these two groups of slices. In the dissociated culture of hippocampal neurons from the Nectin-1-deficient mice, the amplitude and frequency of mIPSCs were indistinguishable from those in the control neurons. Nectin-1 was not localized at or near the GABAergic inhibitory synapses. These results indicate that Nectin-1 regulates the neuronal activities in the CA3 region of the hippocampus by suppressing the GABAergic inhibitory synaptic transmission.
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Nectins and Nectin-Like Molecules in Development and Disease
Current topics in developmental biology, 2015Co-Authors: Kenji Mandai, Masahiro Mori, Yoshiyuki Rikitake, Yoshimi TakaiAbstract:Nectins and Nectin-like molecules (Necls)/Cadms are Ca(2+)-independent immunoglobulin superfamily cell adhesion molecules, expressed in most cell types. Nectins mediate not only homotypic but also heterotypic cell-cell adhesion, in contrast to classic cadherins which participate only in homophilic adhesion. Nectins and Necls function in organogenesis of the eye, inner ear, tooth, and cerebral cortex and in a variety of developmental processes including spermatogenesis, axon guidance, synapse formation, and myelination. They are also involved in various diseases, such as viral infection, hereditary ectodermal dysplasia, Alzheimer's disease, autism spectrum disorder, and cancer. Thus, Nectins and Necls are crucial for both physiology and pathology. This review summarizes recent advances in research on these cell adhesion molecules in development and pathogenesis.
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Cooperation of Nectin-1 and Nectin-3 Is Required for Maintenance of Epidermal Stratification and Proper Hair Shaft Formation in the Mouse
Developmental Biology, 2014Co-Authors: Toshiyuki Yoshida, Yoshimi Takai, Irma ThesleffAbstract:Nectins constitute a family of four cell adhesion molecules which are localized on cell membrane. Mutations in Nectin-1 gene cause the human ectodermal dysplasia syndrome (CLPED1) manifesting severe defects in skin and its appendages. However, Nectin-1 null mutant mice have only a mild defect in epidermal stratification suggesting compensation by other Nectins. We have analysed the epidermal and hair phenotypes of Nectin-1; Nectin-3 compound mutants. Epidermis was fragile and displayed severe defects in stratification, hair follicles were hypoplastic, and hair shaft structure was abnormal. Immunohistochemical analysis revealed severe defects in cell-cell junctions including adherens and tight junctions as well as desmosomes. It is therefore likely that the phenotypes were caused by impaired cell adhesion. The expression patterns of Nectin-1 and Nectin-3 together with the phenotypes in compound mutants indicated that heterophilic interactions between the two Nectins are required for proper formation of epidermis and hair in mice. The Nectin-1; Nectin-3 compound mutant mice partially reproduced the phenotype of human CLPED1 patients.
Wataru Ikeda - One of the best experts on this subject based on the ideXlab platform.
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Nectins and Nectin-like molecules: roles in contact inhibition of cell movement and proliferation
Nature reviews. Molecular cell biology, 2008Co-Authors: Yoshimi Takai, Wataru Ikeda, Jun Miyoshi, Hisakazu OgitaAbstract:Nectins and Nectin-like molecules (Necls) are immunoglobulin-like transmembrane cell adhesion molecules that are expressed in various cell types. Homophilic and heterophilic engagements between family members provide cells with molecular tools for intercellular communications. Nectins primarily regulate cell-cell adhesions, whereas Necls are involved in a greater variety of cellular functions. Recent studies have revealed that Nectins and NECL-5, in cooperation with integrin alphavbeta3 and platelet-derived growth factor receptor, are crucial for the mechanisms that underlie contact inhibition of cell movement and proliferation; this has important implications for the development and tissue regeneration of multicellular organisms and the phenotypes of cancer cells.
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Expression of Nectin-2 in mouse granulosa cells
European journal of obstetrics gynecology and reproductive biology, 2005Co-Authors: Rikako Kawagishi, Wataru Ikeda, Yoshimi Takai, Koji Morimoto, Masahiro Tahara, Kenichiro Morishige, Masahiro Sakata, Keiichi Tasaka, Yuji MurataAbstract:Abstract Objective: The development and maturation of the ovarian follicles are characterized by structural changes that require components involved in cell–cell adhesion systems. Recently a novel group of cell adhesion molecules named Nectins has been identified. The present study examined expression and cell-specific localization of Nectins during mouse follicular development. Study design: Expression of Nectins in mouse ovary was investigated by immnuoblot analysis and immunohistochemistry. More precise localization was determined by electron microscopy. Results: Immunoblot analysis revealed expression of Nectin-2 and Nectin-3 but not Nectin-1 in ovarian granulosa cells. Immunohistochemistry demonstrated expression of Nectin-2 at cell–cell adhesion sites of granulosa cell layer in the primary and preantral follicles. Especially, intense immunoreactivity of Nectin-2 accumulated around the zona pellucida. In antral follicles, the intensity of Nectin-2 expression on granulosa cells was decreased. By electron microscopy Nectin-2 was detected not only on thin extensions of granulosa cells penetrating the zona pellucida, but also on the attachment sites between thin extensions of granulosa cells and oocyte surface. Conclusion: The restricted expression of Nectin-2 in the granulosa cells of primary and preantral follicles might reflect some of the molecular changes in cell–cell adhesion during early follicular development.
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Nectin like molecule 1 tsll1 syncam3 a neural tissue specific immunoglobulin like cell cell adhesion molecule localizing at non junctional contact sites of presynaptic nerve terminals axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Toshihisa Ohtsuka, Akira Mizoguchi, Maki Deguchitawarada, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Maki Deguchi-tawarada, Toshihisa Ohtsuka, Akira Mizoguchi, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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Roles and modes of action of Nectins in cell-cell adhesion.
Seminars in cell & developmental biology, 2004Co-Authors: Kenji Irie, Wataru Ikeda, Kazuya Shimizu, Toshiaki Sakisaka, Yoshimi TakaiAbstract:Nectins are Ca(2+)-independent immunoglobulin (Ig)-like cell-cell adhesion molecules (CAMs), which comprise a family consisting of four members. Each Nectin homophilically and heterophilically trans-interacts and causes cell-cell adhesion. Biochemical, cell biological, and knockout mice studies have revealed that Nectins play important roles in formation of many types of cell-cell junctions and cell-cell contacts, including cadherin-based adherens junctions (AJs) and synapses. Mode of action of Nectins in the formation of AJs has extensively been investigated. Nectins form initial cell-cell adhesion and recruit E-cadherin to the Nectin-based cell-cell adhesion sites. In addition, Nectins induce activation of Cdc42 and Rac small G proteins, which eventually enhances the formation of cadherin-based AJs through the reorganization of the actin cytoskeleton. Nectins furthermore heterophilically trans-interact with Nectin-like molecules (Necls), other Ig-like CAMs, and assist or modify their various functions, such as cell adhesion, migration, and proliferation. We describe here the roles and modes of action of Nectins as CAMs.
Shigeki Kakunaga - One of the best experts on this subject based on the ideXlab platform.
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Nectin like molecule 1 tsll1 syncam3 a neural tissue specific immunoglobulin like cell cell adhesion molecule localizing at non junctional contact sites of presynaptic nerve terminals axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Toshihisa Ohtsuka, Akira Mizoguchi, Maki Deguchitawarada, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Maki Deguchi-tawarada, Toshihisa Ohtsuka, Akira Mizoguchi, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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implications of Nectin like molecule 2 igsf4 ra175 sgigsf tslc1 syncam1 in cell cell adhesion and transmembrane protein localization in epithelial cells
Journal of Biological Chemistry, 2003Co-Authors: Tatsushi Shingai, Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Koji Morimoto, Kyoji Takekuni, Masakazu Takeuchi, Keiko Satoh, Toshio Imai, Morito MondenAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules that play roles in organization of a variety of cell-cell junctions in cooperation with or independently of cadherins. Four Nectins have been identified. Five Nectin-like molecules, which have domain structures similar to those of Nectins, have been identified, and we characterized here Nectin-like molecule-2 (Necl-2)/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1. Necl-2 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-1/TSLL1/SynCAM3 and Nectin-3. Necl-2 was widely expressed in rat tissues examined. Necl-2 localized at the basolateral plasma membrane in epithelial cells of the mouse gall bladder, but not at specialized cell-cell junctions, such as tight junctions, adherens junctions, and desmosomes. Nectins bind afadin, whereas Necl-2 did not bind afadin but bound Pals2, a membrane-associated guanylate kinase family member known to bind Lin-7, implicated in the proper localization of the Let-23 protein in Caenorhabditis elegans, the homologue of mammalian epidermal growth factor receptor. These results indicate the unique localization of Necl-2 and its possible involvement in localization of a transmembrane protein(s) through Pals2.
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tage4 Nectin like molecule 5 heterophilically trans interacts with cell adhesion molecule Nectin 3 and enhances cell migration
Journal of Biological Chemistry, 2003Co-Authors: Wataru Ikeda, Shigeki Kakunaga, Shinsuke Itoh, Koji Morimoto, Kyoji Takekuni, Tatsushi Shingai, Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Masakazu TakeuchiAbstract:Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of Nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with Nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with Nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a Nectin- and actin filament-binding protein that connects Nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with Nectin-3 and regulates cell migration. Tage4 is tentatively re-named here Nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of Nectins.
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Tage4/Nectin-like Molecule-5 Heterophilically trans-Interacts with Cell Adhesion Molecule Nectin-3 and Enhances Cell Migration
The Journal of biological chemistry, 2003Co-Authors: Wataru Ikeda, Shigeki Kakunaga, Shinsuke Itoh, Koji Morimoto, Kyoji Takekuni, Tatsushi Shingai, Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Masakazu TakeuchiAbstract:Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of Nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with Nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with Nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a Nectin- and actin filament-binding protein that connects Nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with Nectin-3 and regulates cell migration. Tage4 is tentatively re-named here Nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of Nectins.
Shinsuke Itoh - One of the best experts on this subject based on the ideXlab platform.
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Nectin like molecule 1 tsll1 syncam3 a neural tissue specific immunoglobulin like cell cell adhesion molecule localizing at non junctional contact sites of presynaptic nerve terminals axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Toshihisa Ohtsuka, Akira Mizoguchi, Maki Deguchitawarada, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Maki Deguchi-tawarada, Toshihisa Ohtsuka, Akira Mizoguchi, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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implications of Nectin like molecule 2 igsf4 ra175 sgigsf tslc1 syncam1 in cell cell adhesion and transmembrane protein localization in epithelial cells
Journal of Biological Chemistry, 2003Co-Authors: Tatsushi Shingai, Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Koji Morimoto, Kyoji Takekuni, Masakazu Takeuchi, Keiko Satoh, Toshio Imai, Morito MondenAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules that play roles in organization of a variety of cell-cell junctions in cooperation with or independently of cadherins. Four Nectins have been identified. Five Nectin-like molecules, which have domain structures similar to those of Nectins, have been identified, and we characterized here Nectin-like molecule-2 (Necl-2)/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1. Necl-2 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-1/TSLL1/SynCAM3 and Nectin-3. Necl-2 was widely expressed in rat tissues examined. Necl-2 localized at the basolateral plasma membrane in epithelial cells of the mouse gall bladder, but not at specialized cell-cell junctions, such as tight junctions, adherens junctions, and desmosomes. Nectins bind afadin, whereas Necl-2 did not bind afadin but bound Pals2, a membrane-associated guanylate kinase family member known to bind Lin-7, implicated in the proper localization of the Let-23 protein in Caenorhabditis elegans, the homologue of mammalian epidermal growth factor receptor. These results indicate the unique localization of Necl-2 and its possible involvement in localization of a transmembrane protein(s) through Pals2.
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tage4 Nectin like molecule 5 heterophilically trans interacts with cell adhesion molecule Nectin 3 and enhances cell migration
Journal of Biological Chemistry, 2003Co-Authors: Wataru Ikeda, Shigeki Kakunaga, Shinsuke Itoh, Koji Morimoto, Kyoji Takekuni, Tatsushi Shingai, Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Masakazu TakeuchiAbstract:Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of Nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with Nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with Nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a Nectin- and actin filament-binding protein that connects Nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with Nectin-3 and regulates cell migration. Tage4 is tentatively re-named here Nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of Nectins.
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Tage4/Nectin-like Molecule-5 Heterophilically trans-Interacts with Cell Adhesion Molecule Nectin-3 and Enhances Cell Migration
The Journal of biological chemistry, 2003Co-Authors: Wataru Ikeda, Shigeki Kakunaga, Shinsuke Itoh, Koji Morimoto, Kyoji Takekuni, Tatsushi Shingai, Keiko Satoh, Yoko Inoue, Akiko Hamaguchi, Masakazu TakeuchiAbstract:Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of Nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with Nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with Nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a Nectin- and actin filament-binding protein that connects Nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with Nectin-3 and regulates cell migration. Tage4 is tentatively re-named here Nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of Nectins.
Akira Mizoguchi - One of the best experts on this subject based on the ideXlab platform.
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Localization of Nectin-2δ at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in Nectin-2 knockout mouse brain.
Brain research, 2016Co-Authors: Muneaki Miyata, Takeshi Fujiwara, Tomohiko Maruo, Kenji Mandai, Shujie Wang, Junya Sato, Hajime Shiotani, Aika Kaito, Yu Itoh, Akira MizoguchiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules. In the nervous system, among four members (Nectin-1, -2, -3, and -4), Nectin-1 and -3 are asymmetrically localized at puncta adherentia junctions formed between the mossy fiber terminals and the dendrites of CA3 pyramidal neurons in the mouse hippocampus and heterophilic trans-interactions between Nectin-1 and Nectin-3 are involved in the selective interaction of axons and dendrites of cultured neurons. By contrast, Nectin-2, which has two splicing variants, Nectin-2α and -2δ, has not been well characterized in the brain. We showed here that Nectin-2α was expressed in both cultured mouse neurons and astrocytes whereas Nectin-2δ was selectively expressed in the astrocytes. Nectin-2δ was localized at the adhesion sites between adjacent cultured astrocytes, but in the brain it was localized on the plasma membranes of astrocytic perivascular endfoot processes facing the basement membrane of blood vessels. Genetic ablation of Nectin-2 caused degeneration of astrocytic perivascular endfoot processes and neurons in the cerebral cortex. These results uncovered for the first time the localization and critical functions of Nectin-2 in the brain.
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Regulatory role of the cell adhesion molecule Nectin-1 in GABAergic inhibitory synaptic transmission in the CA3 region of mouse hippocampus.
Genes to cells : devoted to molecular & cellular mechanisms, 2015Co-Authors: Xiaoqi Geng, Akira Mizoguchi, Yoshimi Takai, Takeshi Fujiwara, Tomohiko Maruo, Kenji Mandai, Shujie Wang, Masahiro MoriAbstract:Proper operation of a neural circuit relies on both excitatory and inhibitory synapses. We previously showed that cell adhesion molecules Nectin-1 and Nectin-3 are localized at puncta adherentia junctions of the hippocampal mossy fiber glutamatergic excitatory synapses and that they do not regulate the excitatory synaptic transmission onto the CA3 pyramidal cells. We studied here the roles of these Nectins in the GABAergic inhibitory synaptic transmission onto the CA3 pyramidal cells using Nectin-1-deficient and Nectin-3-deficient cultured mouse hippocampal slices. In these mutant slices, the amplitudes and frequencies of miniature excitatory postsynaptic currents were indistinguishable from those in the control slices. In the Nectin-1-deficient slices, but not in the Nectin-3-deficient slices, however, the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) was larger than that in the control slices, although the frequency of the mIPSCs was not different between these two groups of slices. In the dissociated culture of hippocampal neurons from the Nectin-1-deficient mice, the amplitude and frequency of mIPSCs were indistinguishable from those in the control neurons. Nectin-1 was not localized at or near the GABAergic inhibitory synapses. These results indicate that Nectin-1 regulates the neuronal activities in the CA3 region of the hippocampus by suppressing the GABAergic inhibitory synaptic transmission.
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aberrant cochlear hair cell attachments caused by Nectin 3 deficiency result in hair bundle abnormalities
Development, 2014Co-Authors: Terunobu Fukuda, Akira Mizoguchi, Shujie Wang, Yoshiyuki Rikitake, Hideru Togashi, Kanoko Kominami, Kenichi Hirata, Yoshimi TakaiAbstract:The organ of Corti consists of sensory hair cells (HCs) interdigitated with nonsensory supporting cells (SCs) to form a checkerboard-like cellular pattern. HCs are equipped with hair bundles on their apical surfaces. We previously reported that cell-adhesive Nectins regulate the checkerboard-like cellular patterning of HCs and SCs in the mouse auditory epithelium. Nectin-1 and -3 are differentially expressed in normal HCs and SCs, respectively, and in Nectin-3-deficient mice a number of HCs are aberrantly attached to each other. We show here that these aberrantly attached HCs in Nectin-3-deficient mice, but not unattached ones, show disturbances of the orientation and morphology of the hair bundles and the positioning of the kinocilium, with additional abnormal localisation of cadherin-catenin complexes and the apical-basal polarity proteins Pals1 and Par-3. These results indicate that, owing to the loss of Nectin-3, hair cells contact each other inappropriately and form abnormal junctions, ultimately resulting in abnormal hair bundle orientation and morphology.
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Nectin like molecule 1 tsll1 syncam3 a neural tissue specific immunoglobulin like cell cell adhesion molecule localizing at non junctional contact sites of presynaptic nerve terminals axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Toshihisa Ohtsuka, Akira Mizoguchi, Maki Deguchitawarada, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
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Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes
Journal of Cell Science, 2005Co-Authors: Shigeki Kakunaga, Wataru Ikeda, Shinsuke Itoh, Maki Deguchi-tawarada, Toshihisa Ohtsuka, Akira Mizoguchi, Yoshimi TakaiAbstract:Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, Nectin-1 and Nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a Nectin- and actin-filament-binding protein. Five Nectin-like molecules (Necls) which have domain structures similar to those of Nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, Nectin-1 and Nectin-3, but not with Necl-5 or Nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
