The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function.
Identifieur interne : 002739 ( Main/Exploration ); précédent : 002738; suivant : 002740The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function.
Auteurs : Jessica K. Mountford [Australie] ; Claire Petitjean [Australie] ; Harun W Kusuma Putra [Australie] ; Jonathan A. Mccafferty [Australie] ; Natasha M. Setiabakti [Australie] ; Hannah Lee [Australie] ; Lotte L. T Nnesen [Australie] ; James D. Mcfadyen [Australie] ; Simone M. Schoenwaelder [Australie] ; Anita Eckly [France] ; Christian Gachet [France] ; Sarah Ellis [Australie] ; Anne K. Voss [Australie] ; Ross A. Dickins [Australie] ; Justin R. Hamilton [Australie] ; Shaun P. Jackson [États-Unis]Source :
- Nature communications [ 2041-1723 ] ; 2015.
Descripteurs français
- KwdFr :
- Adhérence cellulaire, Adhésivité plaquettaire, Agrégation plaquettaire, Allèles, Animaux, Contrainte mécanique, Croisements génétiques, Génotype, Humains, Hémostase, Microscopie électronique à transmission, Mutation, Perfusion, Phosphatidylinositol 3-kinases (métabolisme), Phosphorylation, Plaquettes (métabolisme), Régulation de l'expression des gènes, Résistance au cisaillement, Souris, Souris de lignée C57BL, Thrombose (génétique), Thrombose (métabolisme), Transduction du signal, Transplantation de moelle osseuse.
- MESH :
- génétique : Thrombose.
- métabolisme : Phosphatidylinositol 3-kinases, Plaquettes, Thrombose.
- Adhérence cellulaire, Adhésivité plaquettaire, Agrégation plaquettaire, Allèles, Animaux, Contrainte mécanique, Croisements génétiques, Génotype, Humains, Hémostase, Microscopie électronique à transmission, Mutation, Perfusion, Phosphorylation, Régulation de l'expression des gènes, Résistance au cisaillement, Souris, Souris de lignée C57BL, Transduction du signal, Transplantation de moelle osseuse.
English descriptors
- KwdEn :
- Alleles, Animals, Blood Platelets (metabolism), Bone Marrow Transplantation, Cell Adhesion, Crosses, Genetic, Gene Expression Regulation, Genotype, Hemostasis, Humans, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Mutation, Perfusion, Phosphatidylinositol 3-Kinases (metabolism), Phosphorylation, Platelet Adhesiveness, Platelet Aggregation, Shear Strength, Signal Transduction, Stress, Mechanical, Thrombosis (genetics), Thrombosis (metabolism).
- MESH :
- chemical , metabolism : Phosphatidylinositol 3-Kinases.
- genetics : Thrombosis.
- metabolism : Blood Platelets, Thrombosis.
- Alleles, Animals, Bone Marrow Transplantation, Cell Adhesion, Crosses, Genetic, Gene Expression Regulation, Genotype, Hemostasis, Humans, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Mutation, Perfusion, Phosphorylation, Platelet Adhesiveness, Platelet Aggregation, Shear Strength, Signal Transduction, Stress, Mechanical.
Abstract
PI3KC2α is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover a role for PI3KC2α in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular system) that results in dysregulated platelet adhesion under haemodynamic shear stress. Structural alterations in the platelet internal membrane lead to enhanced membrane tether formation that is associated with accelerated, yet highly unstable, thrombus formation in vitro and in vivo. Notably, agonist-induced 3-phosphorylated phosphoinositide production and cellular activation are normal in PI3KC2α-deficient platelets. These findings demonstrate an important role for PI3KC2α in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling. These studies provide a link between the open canalicular system and platelet adhesive function that has relevance to the primary haemostatic and prothrombotic function of platelets.
DOI: 10.1038/ncomms7535
PubMed: 25779105
Affiliations:
- Australie, France, États-Unis
- Alsace (région administrative), Californie, Grand Est, Victoria (État)
- Melbourne, Strasbourg
- Université de Melbourne, Université de Strasbourg
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002F23
- to stream PubMed, to step Curation: 002E45
- to stream PubMed, to step Checkpoint: 002E45
- to stream Ncbi, to step Merge: 002353
- to stream Ncbi, to step Curation: 002353
- to stream Ncbi, to step Checkpoint: 002353
- to stream Main, to step Merge: 002739
- to stream Main, to step Curation: 002739
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function.</title><author><name sortKey="Mountford, Jessica K" sort="Mountford, Jessica K" uniqKey="Mountford J" first="Jessica K" last="Mountford">Jessica K. Mountford</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Petitjean, Claire" sort="Petitjean, Claire" uniqKey="Petitjean C" first="Claire" last="Petitjean">Claire Petitjean</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Putra, Harun W Kusuma" sort="Putra, Harun W Kusuma" uniqKey="Putra H" first="Harun W Kusuma" last="Putra">Harun W Kusuma Putra</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Mccafferty, Jonathan A" sort="Mccafferty, Jonathan A" uniqKey="Mccafferty J" first="Jonathan A" last="Mccafferty">Jonathan A. Mccafferty</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Setiabakti, Natasha M" sort="Setiabakti, Natasha M" uniqKey="Setiabakti N" first="Natasha M" last="Setiabakti">Natasha M. Setiabakti</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Hannah" sort="Lee, Hannah" uniqKey="Lee H" first="Hannah" last="Lee">Hannah Lee</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="T Nnesen, Lotte L" sort="T Nnesen, Lotte L" uniqKey="T Nnesen L" first="Lotte L" last="T Nnesen">Lotte L. T Nnesen</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Mcfadyen, James D" sort="Mcfadyen, James D" uniqKey="Mcfadyen J" first="James D" last="Mcfadyen">James D. Mcfadyen</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Schoenwaelder, Simone M" sort="Schoenwaelder, Simone M" uniqKey="Schoenwaelder S" first="Simone M" last="Schoenwaelder">Simone M. Schoenwaelder</name><affiliation wicri:level="1"><nlm:affiliation>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050</wicri:regionArea><wicri:noRegion>Newtown 2050</wicri:noRegion></affiliation></author><author><name sortKey="Eckly, Anita" sort="Eckly, Anita" uniqKey="Eckly A" first="Anita" last="Eckly">Anita Eckly</name><affiliation wicri:level="4"><nlm:affiliation>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg</wicri:regionArea><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Gachet, Christian" sort="Gachet, Christian" uniqKey="Gachet C" first="Christian" last="Gachet">Christian Gachet</name><affiliation wicri:level="4"><nlm:affiliation>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg</wicri:regionArea><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Ellis, Sarah" sort="Ellis, Sarah" uniqKey="Ellis S" first="Sarah" last="Ellis">Sarah Ellis</name><affiliation wicri:level="4"><nlm:affiliation>Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Voss, Anne K" sort="Voss, Anne K" uniqKey="Voss A" first="Anne K" last="Voss">Anne K. Voss</name><affiliation wicri:level="4"><nlm:affiliation>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Dickins, Ross A" sort="Dickins, Ross A" uniqKey="Dickins R" first="Ross A" last="Dickins">Ross A. Dickins</name><affiliation wicri:level="4"><nlm:affiliation>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Hamilton, Justin R" sort="Hamilton, Justin R" uniqKey="Hamilton J" first="Justin R" last="Hamilton">Justin R. Hamilton</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Jackson, Shaun P" sort="Jackson, Shaun P" uniqKey="Jackson S" first="Shaun P" last="Jackson">Shaun P. Jackson</name><affiliation wicri:level="2"><nlm:affiliation>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050, Australia [3] Department of Molecular and Experimental Medicine, The Scripps Research Institute, San Diego, CA 92037, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050, Australia [3] Department of Molecular and Experimental Medicine, The Scripps Research Institute, San Diego, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:25779105</idno><idno type="pmid">25779105</idno><idno type="doi">10.1038/ncomms7535</idno><idno type="wicri:Area/PubMed/Corpus">002F23</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002F23</idno><idno type="wicri:Area/PubMed/Curation">002E45</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002E45</idno><idno type="wicri:Area/PubMed/Checkpoint">002E45</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002E45</idno><idno type="wicri:Area/Ncbi/Merge">002353</idno><idno type="wicri:Area/Ncbi/Curation">002353</idno><idno type="wicri:Area/Ncbi/Checkpoint">002353</idno><idno type="wicri:Area/Main/Merge">002739</idno><idno type="wicri:Area/Main/Curation">002739</idno><idno type="wicri:Area/Main/Exploration">002739</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function.</title><author><name sortKey="Mountford, Jessica K" sort="Mountford, Jessica K" uniqKey="Mountford J" first="Jessica K" last="Mountford">Jessica K. Mountford</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Petitjean, Claire" sort="Petitjean, Claire" uniqKey="Petitjean C" first="Claire" last="Petitjean">Claire Petitjean</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Putra, Harun W Kusuma" sort="Putra, Harun W Kusuma" uniqKey="Putra H" first="Harun W Kusuma" last="Putra">Harun W Kusuma Putra</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Mccafferty, Jonathan A" sort="Mccafferty, Jonathan A" uniqKey="Mccafferty J" first="Jonathan A" last="Mccafferty">Jonathan A. Mccafferty</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Setiabakti, Natasha M" sort="Setiabakti, Natasha M" uniqKey="Setiabakti N" first="Natasha M" last="Setiabakti">Natasha M. Setiabakti</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Hannah" sort="Lee, Hannah" uniqKey="Lee H" first="Hannah" last="Lee">Hannah Lee</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="T Nnesen, Lotte L" sort="T Nnesen, Lotte L" uniqKey="T Nnesen L" first="Lotte L" last="T Nnesen">Lotte L. T Nnesen</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Mcfadyen, James D" sort="Mcfadyen, James D" uniqKey="Mcfadyen J" first="James D" last="Mcfadyen">James D. Mcfadyen</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Schoenwaelder, Simone M" sort="Schoenwaelder, Simone M" uniqKey="Schoenwaelder S" first="Simone M" last="Schoenwaelder">Simone M. Schoenwaelder</name><affiliation wicri:level="1"><nlm:affiliation>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050</wicri:regionArea><wicri:noRegion>Newtown 2050</wicri:noRegion></affiliation></author><author><name sortKey="Eckly, Anita" sort="Eckly, Anita" uniqKey="Eckly A" first="Anita" last="Eckly">Anita Eckly</name><affiliation wicri:level="4"><nlm:affiliation>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg</wicri:regionArea><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Gachet, Christian" sort="Gachet, Christian" uniqKey="Gachet C" first="Christian" last="Gachet">Christian Gachet</name><affiliation wicri:level="4"><nlm:affiliation>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité mixte de recherche S949 Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Etablissement Français du Sang-Alsace 67000, Strasbourg</wicri:regionArea><placeName><settlement type="city">Strasbourg</settlement><region type="region" nuts="2">Grand Est</region><region type="old region" nuts="2">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Ellis, Sarah" sort="Ellis, Sarah" uniqKey="Ellis S" first="Sarah" last="Ellis">Sarah Ellis</name><affiliation wicri:level="4"><nlm:affiliation>Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre and The University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Voss, Anne K" sort="Voss, Anne K" uniqKey="Voss A" first="Anne K" last="Voss">Anne K. Voss</name><affiliation wicri:level="4"><nlm:affiliation>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Dickins, Ross A" sort="Dickins, Ross A" uniqKey="Dickins R" first="Ross A" last="Dickins">Ross A. Dickins</name><affiliation wicri:level="4"><nlm:affiliation>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>1] Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia [2] Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Hamilton, Justin R" sort="Hamilton, Justin R" uniqKey="Hamilton J" first="Justin R" last="Hamilton">Justin R. Hamilton</name><affiliation wicri:level="1"><nlm:affiliation>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea><wicri:noRegion>Victoria 3004</wicri:noRegion></affiliation></author><author><name sortKey="Jackson, Shaun P" sort="Jackson, Shaun P" uniqKey="Jackson S" first="Shaun P" last="Jackson">Shaun P. Jackson</name><affiliation wicri:level="2"><nlm:affiliation>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050, Australia [3] Department of Molecular and Experimental Medicine, The Scripps Research Institute, San Diego, CA 92037, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1] Australian Centre for Blood Diseases, Monash University, Level 6, 89 Commercial Road, Melbourne, Victoria 3004, Australia [2] The Heart Research Institute and Charles Perkins Centre, The University of Sydney, Newtown 2050, Australia [3] Department of Molecular and Experimental Medicine, The Scripps Research Institute, San Diego, CA 92037</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Nature communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alleles</term><term>Animals</term><term>Blood Platelets (metabolism)</term><term>Bone Marrow Transplantation</term><term>Cell Adhesion</term><term>Crosses, Genetic</term><term>Gene Expression Regulation</term><term>Genotype</term><term>Hemostasis</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Microscopy, Electron, Transmission</term><term>Mutation</term><term>Perfusion</term><term>Phosphatidylinositol 3-Kinases (metabolism)</term><term>Phosphorylation</term><term>Platelet Adhesiveness</term><term>Platelet Aggregation</term><term>Shear Strength</term><term>Signal Transduction</term><term>Stress, Mechanical</term><term>Thrombosis (genetics)</term><term>Thrombosis (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adhérence cellulaire</term><term>Adhésivité plaquettaire</term><term>Agrégation plaquettaire</term><term>Allèles</term><term>Animaux</term><term>Contrainte mécanique</term><term>Croisements génétiques</term><term>Génotype</term><term>Humains</term><term>Hémostase</term><term>Microscopie électronique à transmission</term><term>Mutation</term><term>Perfusion</term><term>Phosphatidylinositol 3-kinases (métabolisme)</term><term>Phosphorylation</term><term>Plaquettes (métabolisme)</term><term>Régulation de l'expression des gènes</term><term>Résistance au cisaillement</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Thrombose (génétique)</term><term>Thrombose (métabolisme)</term><term>Transduction du signal</term><term>Transplantation de moelle osseuse</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Phosphatidylinositol 3-Kinases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Thrombosis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Thrombose</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Blood Platelets</term><term>Thrombosis</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Phosphatidylinositol 3-kinases</term><term>Plaquettes</term><term>Thrombose</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Alleles</term><term>Animals</term><term>Bone Marrow Transplantation</term><term>Cell Adhesion</term><term>Crosses, Genetic</term><term>Gene Expression Regulation</term><term>Genotype</term><term>Hemostasis</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Microscopy, Electron, Transmission</term><term>Mutation</term><term>Perfusion</term><term>Phosphorylation</term><term>Platelet Adhesiveness</term><term>Platelet Aggregation</term><term>Shear Strength</term><term>Signal Transduction</term><term>Stress, Mechanical</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adhérence cellulaire</term><term>Adhésivité plaquettaire</term><term>Agrégation plaquettaire</term><term>Allèles</term><term>Animaux</term><term>Contrainte mécanique</term><term>Croisements génétiques</term><term>Génotype</term><term>Humains</term><term>Hémostase</term><term>Microscopie électronique à transmission</term><term>Mutation</term><term>Perfusion</term><term>Phosphorylation</term><term>Régulation de l'expression des gènes</term><term>Résistance au cisaillement</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Transduction du signal</term><term>Transplantation de moelle osseuse</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">PI3KC2α is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover a role for PI3KC2α in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular system) that results in dysregulated platelet adhesion under haemodynamic shear stress. Structural alterations in the platelet internal membrane lead to enhanced membrane tether formation that is associated with accelerated, yet highly unstable, thrombus formation in vitro and in vivo. Notably, agonist-induced 3-phosphorylated phosphoinositide production and cellular activation are normal in PI3KC2α-deficient platelets. These findings demonstrate an important role for PI3KC2α in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling. These studies provide a link between the open canalicular system and platelet adhesive function that has relevance to the primary haemostatic and prothrombotic function of platelets.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>États-Unis</li></country><region><li>Alsace (région administrative)</li><li>Californie</li><li>Grand Est</li><li>Victoria (État)</li></region><settlement><li>Melbourne</li><li>Strasbourg</li></settlement><orgName><li>Université de Melbourne</li><li>Université de Strasbourg</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Mountford, Jessica K" sort="Mountford, Jessica K" uniqKey="Mountford J" first="Jessica K" last="Mountford">Jessica K. Mountford</name></noRegion><name sortKey="Dickins, Ross A" sort="Dickins, Ross A" uniqKey="Dickins R" first="Ross A" last="Dickins">Ross A. Dickins</name><name sortKey="Ellis, Sarah" sort="Ellis, Sarah" uniqKey="Ellis S" first="Sarah" last="Ellis">Sarah Ellis</name><name sortKey="Hamilton, Justin R" sort="Hamilton, Justin R" uniqKey="Hamilton J" first="Justin R" last="Hamilton">Justin R. Hamilton</name><name sortKey="Lee, Hannah" sort="Lee, Hannah" uniqKey="Lee H" first="Hannah" last="Lee">Hannah Lee</name><name sortKey="Mccafferty, Jonathan A" sort="Mccafferty, Jonathan A" uniqKey="Mccafferty J" first="Jonathan A" last="Mccafferty">Jonathan A. Mccafferty</name><name sortKey="Mcfadyen, James D" sort="Mcfadyen, James D" uniqKey="Mcfadyen J" first="James D" last="Mcfadyen">James D. Mcfadyen</name><name sortKey="Petitjean, Claire" sort="Petitjean, Claire" uniqKey="Petitjean C" first="Claire" last="Petitjean">Claire Petitjean</name><name sortKey="Putra, Harun W Kusuma" sort="Putra, Harun W Kusuma" uniqKey="Putra H" first="Harun W Kusuma" last="Putra">Harun W Kusuma Putra</name><name sortKey="Schoenwaelder, Simone M" sort="Schoenwaelder, Simone M" uniqKey="Schoenwaelder S" first="Simone M" last="Schoenwaelder">Simone M. Schoenwaelder</name><name sortKey="Setiabakti, Natasha M" sort="Setiabakti, Natasha M" uniqKey="Setiabakti N" first="Natasha M" last="Setiabakti">Natasha M. Setiabakti</name><name sortKey="T Nnesen, Lotte L" sort="T Nnesen, Lotte L" uniqKey="T Nnesen L" first="Lotte L" last="T Nnesen">Lotte L. T Nnesen</name><name sortKey="Voss, Anne K" sort="Voss, Anne K" uniqKey="Voss A" first="Anne K" last="Voss">Anne K. Voss</name></country><country name="France"><region name="Grand Est"><name sortKey="Eckly, Anita" sort="Eckly, Anita" uniqKey="Eckly A" first="Anita" last="Eckly">Anita Eckly</name></region><name sortKey="Gachet, Christian" sort="Gachet, Christian" uniqKey="Gachet C" first="Christian" last="Gachet">Christian Gachet</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Jackson, Shaun P" sort="Jackson, Shaun P" uniqKey="Jackson S" first="Shaun P" last="Jackson">Shaun P. Jackson</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002739 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 002739 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:25779105
|texte= The class II PI 3-kinase, PI3KC2α, links platelet internal membrane structure to shear-dependent adhesive function.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:25779105" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a AustralieFrV1
| This area was generated with Dilib version V0.6.33. |  |