Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

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Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation. / Haining, Elizabeth; Matthews, Alexandra; Noy, Peter; Romanska, Hanna; Harris, Helen; Pike, Jeremy; Morowski, Martina; Gavin, Rebecca; Yang, Jing; Milhiet, P. E.; Berditchevski, Fedor; Nieswandt, Bernhard; Poulter, Natalie; Watson, Steve; Tomlinson, Michael.

In: Platelets, Vol. 28, No. 7, 2017, p. 629-642.

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@article{e25869e1971d4f5b8a4eb73a8c495714,
title = "Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation",
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.",
keywords = "GPVI, Platelet, Single particle analysis, Super-resolution imaging, Tetraspanin, Tspan9",
author = "Elizabeth Haining and Alexandra Matthews and Peter Noy and Hanna Romanska and Helen Harris and Jeremy Pike and Martina Morowski and Rebecca Gavin and Jing Yang and Milhiet, {P. E.} and Fedor Berditchevski and Bernhard Nieswandt and Natalie Poulter and Steve Watson and Michael Tomlinson",
year = "2017",
doi = "10.1080/09537104.2016.1254175",
language = "English",
volume = "28",
pages = "629--642",
journal = "Platelets",
issn = "0953-7104",
publisher = "Taylor & Francis",
number = "7",

}

RIS

TY - JOUR

T1 - Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

AU - Haining, Elizabeth

AU - Matthews, Alexandra

AU - Noy, Peter

AU - Romanska, Hanna

AU - Harris, Helen

AU - Pike, Jeremy

AU - Morowski, Martina

AU - Gavin, Rebecca

AU - Yang, Jing

AU - Milhiet, P. E.

AU - Berditchevski, Fedor

AU - Nieswandt, Bernhard

AU - Poulter, Natalie

AU - Watson, Steve

AU - Tomlinson, Michael

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - GPVI

KW - Platelet

KW - Single particle analysis

KW - Super-resolution imaging

KW - Tetraspanin

KW - Tspan9

U2 - 10.1080/09537104.2016.1254175

DO - 10.1080/09537104.2016.1254175

M3 - Article

VL - 28

SP - 629

EP - 642

JO - Platelets

JF - Platelets

SN - 0953-7104

IS - 7

ER -