G6f-like is an ITAM-containing collagen receptor in thrombocytes.

G6f-like is an ITAM-containing collagen receptor in thrombocytes.
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DOI:
10.1371/journal.pone.0052622
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Watson SP
Watson SP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hughes CE;Radhakrishnan UP;Lordkipanidzé M;Egginton S;Dijkstra JM;Jagadeeswaran P;Watson SP

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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基激活基序(ITAM)。GPVI的交联通过Src和Syk家族激酶的顺序激活以及plc - γ2的激活介导激活。鱼的有核血小板被胶原活化,但缺乏GPVI的同源物。在这项研究中,我们发现胶原蛋白通过Src激酶驱动的途径激活全血和流动条件下的鳟鱼血小板。我们鉴定出Ig受体G6f-like是一种胶原受体,并在细胞系试验中证明它通过细胞质ITAM发出信号。使用morpholino在斑马鱼体内敲除g6f样水平,我们观察到在激光损伤的反应中,静脉和动脉系统的闭塞明显延迟或不存在。因此,g6f样蛋白是鱼类血小板中与生理相关的胶原受体,它通过与哺乳动物GPVI相同的基于itam的信号通路发出信号,为趋同进化提供了一个新的例子。
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.
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