title: G6f-like is an ITAM-containing collagen receptor in thrombocytes.
abstract: 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.
authors.affiliation: Centre for Cardiovascular Sciences, Institute for Biomedical Research, The College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom. c.e.hughes@bham.ac.uk
authors.forename: Craig E
authors.initials: CE
authors.lastname: Hughes
authors.forename: Uvaraj P
authors.initials: UP
authors.lastname: Radhakrishnan
authors.forename: Marie
authors.initials: M
authors.lastname: Lordkipanidzé
authors.forename: Stuart
authors.initials: S
authors.lastname: Egginton
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Dijkstra
authors.forename: Pudur
authors.initials: P
authors.lastname: Jagadeeswaran
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002645:Chickens; D003094:Collagen / Q000378:metabolism; D006487:Hemostasis / Q000235:genetics; D006801:Humans; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation / Q000235:genetics; D054730:Protein Interaction Domains and Motifs; D038981:Receptors, Collagen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D038981:Receptors, Collagen; D003094:Collagen; D019061:src-Family Kinases