Centre for Cardiovascular Sciences, Institute for Biomedical Research, The College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
PLoS One. 2012;7(12):e52622. doi: 10.1371/journal.pone.0052622. Epub 2012 Dec 21.
Collagen activates mammalian platelets through a complex of the immunoglobulin (Ig) receptor GPVI and the Fc receptor γ-chain, which has an immunoreceptor tyrosine-based activation motif (ITAM). Cross-linking of GPVI mediates activation through the sequential activation of Src and Syk family kinases and activation of PLCγ2. Nucleated thrombocytes in fish are activated by collagen but lack an ortholog of GPVI. In this study we show that collagen activates trout thrombocytes in whole blood and under flow conditions through a Src kinase driven pathway. We identify the Ig receptor G6f-like as a collagen receptor and demonstrate in a cell line assay that it signals through its cytoplasmic ITAM. Using a morpholino for in vivo knock-down of G6f-like levels in zebrafish, we observed a marked delay or absence of occlusion of the venous and arterial systems in response to laser injury. Thus, G6f-like is a physiologically relevant collagen receptor in fish thrombocytes which signals through the same ITAM-based signalling pathway as mammalian GPVI, providing a novel example of convergent evolution.
胶原蛋白通过免疫球蛋白 (Ig) 受体 GPVI 和 Fc 受体 γ 链的复合物激活哺乳动物血小板，该复合物具有免疫受体酪氨酸激活基序 (ITAM)。GPVI 的交联通过 Src 和 Syk 家族激酶的顺序激活以及 PLCγ2 的激活来介导激活。鱼类有核血小板通过胶原蛋白激活，但缺乏 GPVI 的同源物。在这项研究中，我们表明胶原蛋白通过Src 激酶驱动的途径在全血和流动条件下激活鳟鱼血小板。我们确定 Ig 受体 G6f 样作为胶原蛋白受体，并在细胞系测定中证明它通过其细胞质 ITAM 发出信号。使用斑马鱼体内的一种用于 G6f 样水平的体内敲低的吗啉代寡核苷酸，我们观察到对激光损伤的静脉和动脉系统的闭塞明显延迟或缺失。因此，G6f 样是鱼类血小板中一种生理相关的胶原蛋白受体，它通过与哺乳动物 GPVI 相同的基于 ITAM 的信号通路发出信号，提供了趋同进化的新范例。
