G6f-Like Is an ITAM-Containing Collagen Receptor in Thrombocytes

Craig E. Hughes, Uvaraj P. Radhakrishnan, Marie Lordkipanidzé, Stuart Egginton, Johannes M. Dijkstra, Pudur Jagadeeswaran, Stephen P. Watson

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere52622
JournalPloS one
Volume7
Issue number12
DOIs
Publication statusPublished - 21-12-2012

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Immunoreceptor Tyrosine-Based Activation Motif
Collagen Receptors
blood platelets
Tyrosine
tyrosine
collagen
Blood Platelets
Chemical activation
receptors
Collagen
src-Family Kinases
Immunoglobulins
Fishes
immunoglobulins
phosphotransferases (kinases)
Morpholinos
Fish
Fc Receptors
Trout
Zebrafish

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hughes, C. E., Radhakrishnan, U. P., Lordkipanidzé, M., Egginton, S., Dijkstra, J. M., Jagadeeswaran, P., & Watson, S. P. (2012). G6f-Like Is an ITAM-Containing Collagen Receptor in Thrombocytes. PloS one, 7(12), [e52622]. https://doi.org/10.1371/journal.pone.0052622
Hughes, Craig E. ; Radhakrishnan, Uvaraj P. ; Lordkipanidzé, Marie ; Egginton, Stuart ; Dijkstra, Johannes M. ; Jagadeeswaran, Pudur ; Watson, Stephen P. / G6f-Like Is an ITAM-Containing Collagen Receptor in Thrombocytes. In: PloS one. 2012 ; Vol. 7, No. 12.
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Hughes, CE, Radhakrishnan, UP, Lordkipanidzé, M, Egginton, S, Dijkstra, JM, Jagadeeswaran, P & Watson, SP 2012, 'G6f-Like Is an ITAM-Containing Collagen Receptor in Thrombocytes', PloS one, vol. 7, no. 12, e52622. https://doi.org/10.1371/journal.pone.0052622

G6f-Like Is an ITAM-Containing Collagen Receptor in Thrombocytes. / Hughes, Craig E.; Radhakrishnan, Uvaraj P.; Lordkipanidzé, Marie; Egginton, Stuart; Dijkstra, Johannes M.; Jagadeeswaran, Pudur; Watson, Stephen P.

In: PloS one, Vol. 7, No. 12, e52622, 21.12.2012.

Research output: Contribution to journalArticle

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Hughes CE, Radhakrishnan UP, Lordkipanidzé M, Egginton S, Dijkstra JM, Jagadeeswaran P et al. G6f-Like Is an ITAM-Containing Collagen Receptor in Thrombocytes. PloS one. 2012 Dec 21;7(12). e52622. https://doi.org/10.1371/journal.pone.0052622