Connexin40 regulates platelet function
Identifieur interne : 003763 ( Main/Curation ); précédent : 003762; suivant : 003764Connexin40 regulates platelet function
Auteurs : Sakthivel Vaiyapuri [Royaume-Uni] ; Leonardo A. Moraes [Royaume-Uni] ; Tanya Sage [Royaume-Uni] ; Marfoua S. Ali [Royaume-Uni] ; Kirsty R. Lewis [Royaume-Uni] ; Martyn P. Mahaut-Smith [Royaume-Uni] ; Ernesto Oviedo-Orta [Royaume-Uni] ; Alexander M. Simon [États-Unis] ; Jonathan M. Gibbins [Royaume-Uni]Source :
- Nature Communications [ 2041-1723 ] ; 2013.
Abstract
The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor 37,43Gap27 on
Url:
DOI: 10.1038/ncomms3564
PubMed: 24096827
PubMed Central: 3806366
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Moraes</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading</institution>, Harborne Building, Whiteknights, RG6 6AS Reading,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sage, Tanya" sort="Sage, Tanya" uniqKey="Sage T" first="Tanya" last="Sage">Tanya Sage</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading</institution>, Harborne Building, Whiteknights, RG6 6AS Reading,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ali, Marfoua S" sort="Ali, Marfoua S" uniqKey="Ali M" first="Marfoua S." last="Ali">Marfoua S. Ali</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading</institution>, Harborne Building, Whiteknights, RG6 6AS Reading,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lewis, Kirsty R" sort="Lewis, Kirsty R" uniqKey="Lewis K" first="Kirsty R." last="Lewis">Kirsty R. Lewis</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading</institution>, Harborne Building, Whiteknights, RG6 6AS Reading,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mahaut Smith, Martyn P" sort="Mahaut Smith, Martyn P" uniqKey="Mahaut Smith M" first="Martyn P." last="Mahaut-Smith">Martyn P. Mahaut-Smith</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Cell Physiology and Pharmacology, University of Leicester</institution>, Leicester, LE1 9HN,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Oviedo Orta, Ernesto" sort="Oviedo Orta, Ernesto" uniqKey="Oviedo Orta E" first="Ernesto" last="Oviedo-Orta">Ernesto Oviedo-Orta</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Faculty of Health and Medical Sciences, Cardiovascular Biology Research, University of Surrey</institution>, Guildford GU2 7XH,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Simon, Alexander M" sort="Simon, Alexander M" uniqKey="Simon A" first="Alexander M." last="Simon">Alexander M. Simon</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Physiology, University of Arizona</institution>, Tucson, Arizona 85724-5051,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gibbins, Jonathan M" sort="Gibbins, Jonathan M" uniqKey="Gibbins J" first="Jonathan M." last="Gibbins">Jonathan M. Gibbins</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading</institution>, Harborne Building, Whiteknights, RG6 6AS Reading,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor <sup>37,43</sup>Gap27 on <italic>Cx40</italic><sup><italic>−/−</italic></sup> mouse platelets and of the Cx40 inhibitor <sup>40</sup>Gap27 on <italic>Cx37</italic><sup><italic>−/−</italic></sup> mouse platelets revealed that each connexin is able to function independently. Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating the physiological importance of this protein in platelets. We conclude that multiple connexins are involved in regulating platelet function, thereby contributing to haemostasis and thrombosis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Goodenough, D A" uniqKey="Goodenough D">D. A. Goodenough</name></author><author><name sortKey="Paul, D L" uniqKey="Paul D">D. L. Paul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodenough, D A" uniqKey="Goodenough D">D. A. Goodenough</name></author><author><name sortKey="Paul, D L" uniqKey="Paul D">D. L. Paul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="John, S" uniqKey="John S">S. John</name></author><author><name sortKey="Cesario, D" uniqKey="Cesario D">D. Cesario</name></author><author><name sortKey="Weiss, J N" uniqKey="Weiss J">J. N. Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goodenough, D A" uniqKey="Goodenough D">D. A. 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Li</name></author><author><name sortKey="Paul, D L" uniqKey="Paul D">D. L. Paul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanady, J D" uniqKey="Kanady J">J. D. Kanady</name></author><author><name sortKey="Dellinger, M T" uniqKey="Dellinger M">M. T. Dellinger</name></author><author><name sortKey="Munger, S J" uniqKey="Munger S">S. J. Munger</name></author><author><name sortKey="Witte, M H" uniqKey="Witte M">M. H. Witte</name></author><author><name sortKey="Simon, A M" uniqKey="Simon A">A. M. Simon</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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