Connexin40 regulates platelet function

Sakthivel Vaiyapuri, Leonardo A. Moraes, Tanya Sage, Marfoua S. Ali, Kirsty R. Lewis, Martyn P. Mahaut-Smith, Ernesto Oviedo-Orta, Alex Simon, Jonathan M. Gibbins

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 Cx40-/- mouse platelets and of the Cx40 inhibitor 40Gap27 on Cx37-/- 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.

Original languageEnglish (US)
Article number2564
JournalNature Communications
Volume4
DOIs
StatePublished - 2013

Fingerprint

Platelets
platelets
Blood Platelets
Connexins
mice
hemostatics
inhibitors
deletion
Clot Retraction
Gap Junctions
Platelet Aggregation Inhibitors
thrombosis
Hemostatics
fibrinogen
Hemostasis
Platelet Aggregation
secretions
Fibrinogen
Thrombosis
Agglomeration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Vaiyapuri, S., Moraes, L. A., Sage, T., Ali, M. S., Lewis, K. R., Mahaut-Smith, M. P., ... Gibbins, J. M. (2013). Connexin40 regulates platelet function. Nature Communications, 4, [2564]. https://doi.org/10.1038/ncomms3564

Connexin40 regulates platelet function. / Vaiyapuri, Sakthivel; Moraes, Leonardo A.; Sage, Tanya; Ali, Marfoua S.; Lewis, Kirsty R.; Mahaut-Smith, Martyn P.; Oviedo-Orta, Ernesto; Simon, Alex; Gibbins, Jonathan M.

In: Nature Communications, Vol. 4, 2564, 2013.

Research output: Contribution to journalArticle

Vaiyapuri, S, Moraes, LA, Sage, T, Ali, MS, Lewis, KR, Mahaut-Smith, MP, Oviedo-Orta, E, Simon, A & Gibbins, JM 2013, 'Connexin40 regulates platelet function', Nature Communications, vol. 4, 2564. https://doi.org/10.1038/ncomms3564
Vaiyapuri S, Moraes LA, Sage T, Ali MS, Lewis KR, Mahaut-Smith MP et al. Connexin40 regulates platelet function. Nature Communications. 2013;4. 2564. https://doi.org/10.1038/ncomms3564
Vaiyapuri, Sakthivel ; Moraes, Leonardo A. ; Sage, Tanya ; Ali, Marfoua S. ; Lewis, Kirsty R. ; Mahaut-Smith, Martyn P. ; Oviedo-Orta, Ernesto ; Simon, Alex ; Gibbins, Jonathan M. / Connexin40 regulates platelet function. In: Nature Communications. 2013 ; Vol. 4.
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