Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

Elizabeth Haining, Alexandra Matthews, Peter Noy, Hanna Romanska, Helen Harris, Jeremy Pike, Martina Morowski, Rebecca Gavin, Jing Yang, P. E. Milhiet, Fedor Berditchevski, Bernhard Nieswandt, Natalie Poulter, Steve Watson, Michael Tomlinson

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
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Abstract

The tetraspanins are a superfamily of four-transmembrane proteins which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterized gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels. A GPVI activation defect was suggested by partially impaired GPVI-induced protein tyrosine phosphorylation. In mechanistic experiments, Tspan9 and GPVI co-immunoprecipitated and co-localized, but super-resolution imaging revealed no defects in collagen-induced GPVI clustering on Tspan9-deficient platelets. However, single particle tracking using total internal reflection fluorescence microscopy showed that GPVI lateral diffusion was reduced by approximately 50% in the absence of Tspan9. Therefore Tspan9 plays a fine-tuning role in platelet activation by regulating GPVI membrane dynamics.
Original languageEnglish
Pages (from-to)629-642
JournalPlatelets
Volume28
Issue number7
Early online date29 Dec 2016
DOIs
Publication statusPublished - 2017

Keywords

  • GPVI
  • Platelet
  • Single particle analysis
  • Super-resolution imaging
  • Tetraspanin
  • Tspan9

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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