期刊
PLATELETS
卷 32, 期 7, 页码 888-894出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/09537104.2021.1902971
关键词
Platelets; Ion Channel; Connexin; Pannexin-1; Gap junction
资金
- British Heart Foundation [FS/17/31/32848, PG/17/76/33082]
Connexins and Pannexins are families of proteins expressed widely in mammalian cells, forming channels that play a role in intercellular signaling. In platelets, pannexin-1 and connexins are involved in non-vesicular ATP release and have the potential to be drug targets for arterial thrombosis management, as their activation is regulated by physiological stimuli such as mechanical stimulation.
Connexins are a family of gap junction forming proteins widely expressed by mammalian cells. They assemble into hexameric hemichannels, which can either function independently or dock with opposing hemichannels on apposite cells, forming a gap junction. Pannexins are structurally related to the connexins but extensive glycosylation of these channels prevents docking to form gap junctions and they function as membrane channels. Platelets express pannexin-1 and several connexin family members (Cx37, Cx40 and Cx62). These channels are permeable to molecules up to 1,000 Daltons in molecular mass and functional studies demonstrate their role in non-vesicular ATP release. Channel activation is regulated by (patho)physiological stimuli, such as mechanical stimulation, making them attractive potential drug targets for the management of arterial thrombosis. This review explores the structure and function of platelet pannexin-1 and connexins, the mechanisms by which they are gated and their therapeutic potential.
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