Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

Research output: Contribution to journalArticle

Authors

External organisations

  • Department of Pathology, Medical University of Lodz, Poland
  • Department of Experimental Biomedicine; University Hospital, University of Würzburg; Würzburg Germany
  • INSERM 1054, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier University, France

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.

Details

Original languageEnglish
Pages (from-to)629-642
JournalPlatelets
Volume28
Issue number7
Early online date29 Dec 2016
Publication statusPublished - 2017

Keywords

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