RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src-mediated phosphorylation of cortactin.
Identifieur interne : 001886 ( Ncbi/Curation ); précédent : 001885; suivant : 001887RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src-mediated phosphorylation of cortactin.
Auteurs : Marta Truffi [France] ; Véronique Dubreuil [France] ; Xuan Liang [Australie] ; Nathalie Vacaresse [Danemark] ; Fabienne Nigon [France] ; Siew Ping Han [Australie] ; Alpha S. Yap [Australie] ; Guillermo A. Gomez [Australie] ; Jan Sap [France]Source :
- Journal of cell science [ 1477-9137 ] ; 2014.
Descripteurs français
- KwdFr :
- Actines (métabolisme), Adhérence cellulaire (génétique), Cadhérines (métabolisme), Cellules Caco-2, Cellules HEK293, Cellules épithéliales (physiologie), Cortactine (génétique), Cortactine (métabolisme), Humains, Jonctions adhérentes (génétique), Jonctions adhérentes (métabolisme), Mutation (génétique), Organogenèse (génétique), Petit ARN interférent (génétique), Phosphorylation (génétique), Receptor-Like Protein Tyrosine Phosphatases, Class 4 (génétique), Receptor-Like Protein Tyrosine Phosphatases, Class 4 (métabolisme), Techniques de culture d'organes, Transduction du signal (génétique), Transport de protéines, src-Family kinases (métabolisme).
- MESH :
- génétique : Adhérence cellulaire, Cortactine, Jonctions adhérentes, Mutation, Organogenèse, Petit ARN interférent, Phosphorylation, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Transduction du signal.
- métabolisme : Actines, Cadhérines, Cortactine, Jonctions adhérentes, Receptor-Like Protein Tyrosine Phosphatases, Class 4, src-Family kinases.
- physiologie : Cellules épithéliales.
- Cellules Caco-2, Cellules HEK293, Humains, Techniques de culture d'organes, Transport de protéines.
English descriptors
- KwdEn :
- Actins (metabolism), Adherens Junctions (genetics), Adherens Junctions (metabolism), Caco-2 Cells, Cadherins (metabolism), Cell Adhesion (genetics), Cortactin (genetics), Cortactin (metabolism), Epithelial Cells (physiology), HEK293 Cells, Humans, Mutation (genetics), Organ Culture Techniques, Organogenesis (genetics), Phosphorylation (genetics), Protein Transport, RNA, Small Interfering (genetics), Receptor-Like Protein Tyrosine Phosphatases, Class 4 (genetics), Receptor-Like Protein Tyrosine Phosphatases, Class 4 (metabolism), Signal Transduction (genetics), src-Family Kinases (metabolism).
- MESH :
- chemical , genetics : Cortactin, RNA, Small Interfering, Receptor-Like Protein Tyrosine Phosphatases, Class 4.
- chemical , metabolism : Actins, Cadherins, Cortactin, Receptor-Like Protein Tyrosine Phosphatases, Class 4, src-Family Kinases.
- genetics : Adherens Junctions, Cell Adhesion, Mutation, Organogenesis, Phosphorylation, Signal Transduction.
- metabolism : Adherens Junctions.
- physiology : Epithelial Cells.
- Caco-2 Cells, HEK293 Cells, Humans, Organ Culture Techniques, Protein Transport.
Abstract
Epithelial junctions are fundamental determinants of tissue organization, subject to regulation by tyrosine phosphorylation. Homophilic binding of E-cadherin activates tyrosine kinases, such as Src, that control junctional integrity. Protein tyrosine phosphatases (PTPs) also contribute to cadherin-based adhesion and signaling, but little is known about their specific identity or functions at epithelial junctions. Here, we report that the receptor PTP RPTPα (human gene name PTPRA) is recruited to epithelial adherens junctions at the time of cell-cell contact, where it is in molecular proximity to E-cadherin. RPTPα is required for appropriate cadherin-dependent adhesion and for cyst architecture in three-dimensional culture. Loss of RPTPα impairs adherens junction integrity, as manifested by defective E-cadherin accumulation and peri-junctional F-actin density. These effects correlate with a role for RPTPα in cellular (c)-Src activation at sites of E-cadherin engagement. Mechanistically, RPTPα is required for appropriate tyrosine phosphorylation of cortactin, a major Src substrate and a cytoskeletal actin organizer. Expression of a phosphomimetic cortactin mutant in RPTPα-depleted cells partially rescues F-actin and E-cadherin accumulation at intercellular contacts. These findings indicate that RPTPα controls cadherin-mediated signaling by linking homophilic E-cadherin engagement to cortactin tyrosine phosphorylation through c-Src.
DOI: 10.1242/jcs.134379
PubMed: 24652832
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pubmed:24652832Le document en format XML
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Innovation Centre and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Biotech Research and Innovation Centre and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N</wicri:regionArea><wicri:noRegion>2200 Copenhagen N</wicri:noRegion></affiliation></author><author><name sortKey="Nigon, Fabienne" sort="Nigon, Fabienne" uniqKey="Nigon F" first="Fabienne" last="Nigon">Fabienne Nigon</name><affiliation wicri:level="1"><nlm:affiliation>Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Bâtiment Lamarck, Case 7042, 35 Rue Hélène Brion, F-75205 Paris Cedex 13, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 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Yap</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072</wicri:regionArea><wicri:noRegion>Brisbane 4072</wicri:noRegion></affiliation></author><author><name sortKey="Gomez, Guillermo A" sort="Gomez, Guillermo A" uniqKey="Gomez G" first="Guillermo A" last="Gomez">Guillermo A. Gomez</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Division of Molecular Cell Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072</wicri:regionArea><wicri:noRegion>Brisbane 4072</wicri:noRegion></affiliation></author><author><name sortKey="Sap, Jan" sort="Sap, Jan" uniqKey="Sap J" first="Jan" last="Sap">Jan Sap</name><affiliation wicri:level="1"><nlm:affiliation>Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Bâtiment Lamarck, Case 7042, 35 Rue Hélène Brion, F-75205 Paris Cedex 13, France Biotech Research and Innovation Centre and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark veronique.dubrueil@univ-paris-diderot.fr jansap@fastmail.fm.</nlm:affiliation><country wicri:rule="url">France</country><wicri:regionArea>Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate, UMR 7216 CNRS, Bâtiment Lamarck, Case 7042, 35 Rue Hélène Brion, F-75205 Paris Cedex 13, France Biotech Research and Innovation Centre and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N</wicri:regionArea><wicri:noRegion>2200 Copenhagen N</wicri:noRegion><wicri:noRegion>2200 Copenhagen N</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of cell science</title><idno type="eISSN">1477-9137</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Actins (metabolism)</term><term>Adherens Junctions (genetics)</term><term>Adherens Junctions (metabolism)</term><term>Caco-2 Cells</term><term>Cadherins (metabolism)</term><term>Cell Adhesion (genetics)</term><term>Cortactin (genetics)</term><term>Cortactin (metabolism)</term><term>Epithelial Cells (physiology)</term><term>HEK293 Cells</term><term>Humans</term><term>Mutation (genetics)</term><term>Organ Culture Techniques</term><term>Organogenesis (genetics)</term><term>Phosphorylation (genetics)</term><term>Protein Transport</term><term>RNA, Small Interfering (genetics)</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4 (genetics)</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4 (metabolism)</term><term>Signal Transduction (genetics)</term><term>src-Family Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Actines (métabolisme)</term><term>Adhérence cellulaire (génétique)</term><term>Cadhérines (métabolisme)</term><term>Cellules Caco-2</term><term>Cellules HEK293</term><term>Cellules épithéliales (physiologie)</term><term>Cortactine (génétique)</term><term>Cortactine (métabolisme)</term><term>Humains</term><term>Jonctions adhérentes (génétique)</term><term>Jonctions adhérentes (métabolisme)</term><term>Mutation (génétique)</term><term>Organogenèse (génétique)</term><term>Petit ARN interférent (génétique)</term><term>Phosphorylation (génétique)</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4 (génétique)</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4 (métabolisme)</term><term>Techniques de culture d'organes</term><term>Transduction du signal (génétique)</term><term>Transport de protéines</term><term>src-Family kinases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cortactin</term><term>RNA, Small Interfering</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Actins</term><term>Cadherins</term><term>Cortactin</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4</term><term>src-Family Kinases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adherens Junctions</term><term>Cell Adhesion</term><term>Mutation</term><term>Organogenesis</term><term>Phosphorylation</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adhérence cellulaire</term><term>Cortactine</term><term>Jonctions adhérentes</term><term>Mutation</term><term>Organogenèse</term><term>Petit ARN interférent</term><term>Phosphorylation</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adherens Junctions</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Actines</term><term>Cadhérines</term><term>Cortactine</term><term>Jonctions adhérentes</term><term>Receptor-Like Protein Tyrosine Phosphatases, Class 4</term><term>src-Family kinases</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules épithéliales</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Epithelial Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Caco-2 Cells</term><term>HEK293 Cells</term><term>Humans</term><term>Organ Culture Techniques</term><term>Protein Transport</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules Caco-2</term><term>Cellules HEK293</term><term>Humains</term><term>Techniques de culture d'organes</term><term>Transport de protéines</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Epithelial junctions are fundamental determinants of tissue organization, subject to regulation by tyrosine phosphorylation. Homophilic binding of E-cadherin activates tyrosine kinases, such as Src, that control junctional integrity. Protein tyrosine phosphatases (PTPs) also contribute to cadherin-based adhesion and signaling, but little is known about their specific identity or functions at epithelial junctions. Here, we report that the receptor PTP RPTPα (human gene name PTPRA) is recruited to epithelial adherens junctions at the time of cell-cell contact, where it is in molecular proximity to E-cadherin. RPTPα is required for appropriate cadherin-dependent adhesion and for cyst architecture in three-dimensional culture. Loss of RPTPα impairs adherens junction integrity, as manifested by defective E-cadherin accumulation and peri-junctional F-actin density. These effects correlate with a role for RPTPα in cellular (c)-Src activation at sites of E-cadherin engagement. Mechanistically, RPTPα is required for appropriate tyrosine phosphorylation of cortactin, a major Src substrate and a cytoskeletal actin organizer. Expression of a phosphomimetic cortactin mutant in RPTPα-depleted cells partially rescues F-actin and E-cadherin accumulation at intercellular contacts. These findings indicate that RPTPα controls cadherin-mediated signaling by linking homophilic E-cadherin engagement to cortactin tyrosine phosphorylation through c-Src.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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