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Publication : Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation.

First Author  Haining EJ Year  2017
Journal  Platelets Volume  28
Issue  7 Pages  629-642
PubMed ID  28032533 Mgi Jnum  J:256075
Mgi Id  MGI:6109118 Doi  10.1080/09537104.2016.1254175
Citation  Haining EJ, et al. (2017) Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation. Platelets 28(7):629-642
abstractText  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 characterised 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-localised, 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.
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