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A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic P2Y12 receptor in platelets

Makkawi, M, Howells, D ORCID: 0000-0002-2512-7724, Wright, MD and Jackson, DE 2018 , 'A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic P2Y12 receptor in platelets' , Thrombosis Research, vol. 161 , pp. 12-21 , doi: 10.1016/j.thromres.2017.11.009.

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Abstract

Tumor-suppressing subchromosomal transferable fragment cDNA 6 (TSSC6) expression is restricted to hematopoietic organs and tissues where it plays a role in hematopoietic-cell function. The ADP purinergic receptor P2Y12 is mainly expressed by platelets with important clinical significance as a target for several clinically approved antithrombotic agents. We have previously shown a physical association between P2Y12 and TSSC6 in platelets. Hence our aim was to investigate whether this physical association is translated to functional effects. To investigate this possibility, we used wild-type or TSSC6 knockout (KO) mice treated with either PBS or 50mg/kg clopidogrel. TSSC6 KO mice treated with clopidogrel exhibited synergy in delayed kinetics of clot retraction, reduced collagen-mediated platelet aggregation, and platelet spreading on fibrinogen. Platelets derived from TSSC6 mice with P2Y12 blockade form smaller thrombi when perfused over a collagen matrix under arterial flow. Clopidogrel treated TSSC6 KO arterioles showed smaller and less stable thrombi with increased tendency to embolise in vivo. These studies demonstrate a complementary role between TSSC6 and P2Y12 receptor in platelets in regulating 'outside in' integrin αIIbβ3 signalling thrombus growth and stability.

Item Type: Article
Authors/Creators:Makkawi, M and Howells, D and Wright, MD and Jackson, DE
Keywords: platelets, TSSC6, mice, clopidogrel, purinergic P2Y12
Journal or Publication Title: Thrombosis Research
Publisher: Pergamon Press
ISSN: 0049-3848
DOI / ID Number: 10.1016/j.thromres.2017.11.009
Copyright Information:

Copyright 2017 Elsevier Ltd.

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