Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-10-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2016.1254175 |
| _version_ | 1797684259340681216 |
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| author | Elizabeth J. Haining Alexandra L. Matthews Peter J. Noy Hanna M. Romanska Helen J. Harris Jeremy Pike Martina Morowski Rebecca L. Gavin Jing Yang Pierre-Emmanuel Milhiet Fedor Berditchevski Bernhard Nieswandt Natalie S. Poulter Steve P. Watson Michael G. Tomlinson |
| author_facet | Elizabeth J. Haining Alexandra L. Matthews Peter J. Noy Hanna M. Romanska Helen J. Harris Jeremy Pike Martina Morowski Rebecca L. Gavin Jing Yang Pierre-Emmanuel Milhiet Fedor Berditchevski Bernhard Nieswandt Natalie S. Poulter Steve P. Watson Michael G. Tomlinson |
| author_sort | Elizabeth J. Haining |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:28:03Z |
| format | Article |
| id | doaj.art-450db8670693458ca5e511caed983da9 |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:28:03Z |
| publishDate | 2017-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-450db8670693458ca5e511caed983da92023-09-15T10:31:56ZengTaylor & Francis GroupPlatelets0953-71041369-16352017-10-0128762964210.1080/09537104.2016.12541751254175Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activationElizabeth J. Haining0Alexandra L. Matthews1Peter J. Noy2Hanna M. Romanska3Helen J. Harris4Jeremy Pike5Martina Morowski6Rebecca L. Gavin7Jing Yang8Pierre-Emmanuel Milhiet9Fedor Berditchevski10Bernhard Nieswandt11Natalie S. Poulter12Steve P. Watson13Michael G. Tomlinson14University of BirminghamUniversity of BirminghamUniversity of BirminghamMedical University of ŁódźUniversity of BirminghamUniversity of BirminghamUniversity of Würzburg, WürzburgUniversity of BirminghamUniversity of BirminghamMontpellier UniversityUniversity of BirminghamUniversity of Würzburg, WürzburgUniversity of BirminghamUniversity of BirminghamUniversity of BirminghamThe 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.http://dx.doi.org/10.1080/09537104.2016.1254175gpviplateletsingle particle analysissuper-resolution imagingtetraspanintspan9 |
| spellingShingle | Elizabeth J. Haining Alexandra L. Matthews Peter J. Noy Hanna M. Romanska Helen J. Harris Jeremy Pike Martina Morowski Rebecca L. Gavin Jing Yang Pierre-Emmanuel Milhiet Fedor Berditchevski Bernhard Nieswandt Natalie S. Poulter Steve P. Watson Michael G. Tomlinson Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation Platelets gpvi platelet single particle analysis super-resolution imaging tetraspanin tspan9 |
| title | Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation |
| title_full | Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation |
| title_fullStr | Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation |
| title_full_unstemmed | Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation |
| title_short | Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation |
| title_sort | tetraspanin tspan9 regulates platelet collagen receptor gpvi lateral diffusion and activation |
| topic | gpvi platelet single particle analysis super-resolution imaging tetraspanin tspan9 |
| url | http://dx.doi.org/10.1080/09537104.2016.1254175 |
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