TY - JOUR
T1 - Connexin40 regulates platelet function
AU - Vaiyapuri, Sakthivel
AU - Moraes, Leonardo A.
AU - Sage, Tanya
AU - Ali, Marfoua S.
AU - Lewis, Kirsty R.
AU - Mahaut-Smith, Martyn P.
AU - Oviedo-Orta, Ernesto
AU - Simon, Alexander M.
AU - Gibbins, Jonathan M.
N1 - Funding Information:
This work was supported by the British Heart Foundation (grants: PG/11/125/29320 and RG/09/011/28094); Wellcome Trust, UK; and the National Institutes of Health (grant HL64232).
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms3564
DO - 10.1038/ncomms3564
M3 - Article
C2 - 24096827
AN - SCOPUS:84893350811
SN - 2041-1723
VL - 4
JO - Nature communications
JF - Nature communications
M1 - 2564
ER -