Projects per year
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 language | English |
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Pages (from-to) | 629-642 |
Journal | Platelets |
Volume | 28 |
Issue number | 7 |
Early online date | 29 Dec 2016 |
DOIs | |
Publication status | Published - 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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- 3 Finished
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Regulation of the store-operated Ca2+ entry channel Orai1 by platelet tetraspanin Tspan18
1/07/14 → 30/06/17
Project: Research
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Regulation of platelet and endothelial cell surface receptors by tetraspanin microdomains
1/01/09 → 31/12/13
Project: Research