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Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains
Platelets are essential for wound healing and inflammatory processes, but can also play a deleterious role by causing heart attack and stroke. Normal platelet activation is dependent on tetraspanins, a superfamily of glycoproteins that function as ‘organisers’ of cell membranes by recruiting other r...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652832/ https://www.ncbi.nlm.nih.gov/pubmed/18795891 http://dx.doi.org/10.1042/BJ20081126 |
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author | Protty, Majd B. Watkins, Nicholas A. Colombo, Dario Thomas, Steven G. Heath, Victoria L. Herbert, John M. J. Bicknell, Roy Senis, Yotis A. Ashman, Leonie K. Berditchevski, Fedor Ouwehand, Willem H. Watson, Steve P. Tomlinson, Michael G. |
author_facet | Protty, Majd B. Watkins, Nicholas A. Colombo, Dario Thomas, Steven G. Heath, Victoria L. Herbert, John M. J. Bicknell, Roy Senis, Yotis A. Ashman, Leonie K. Berditchevski, Fedor Ouwehand, Willem H. Watson, Steve P. Tomlinson, Michael G. |
author_sort | Protty, Majd B. |
collection | PubMed |
description | Platelets are essential for wound healing and inflammatory processes, but can also play a deleterious role by causing heart attack and stroke. Normal platelet activation is dependent on tetraspanins, a superfamily of glycoproteins that function as ‘organisers’ of cell membranes by recruiting other receptors and signalling proteins into tetraspanin-enriched microdomains. However, our understanding of how tetraspanin microdomains regulate platelets is hindered by the fact that only four of the 33 mammalian tetraspanins have been identified in platelets. This is because of a lack of antibodies to most tetraspanins and difficulties in measuring mRNA, due to low levels in this anucleate cell. To identify potentially platelet-expressed tetraspanins, mRNA was measured in their nucleated progenitor cell, the megakaryocyte, using serial analysis of gene expression and DNA microarrays. Amongst 19 tetraspanins identified in megakaryocytes, Tspan9, a previously uncharacterized tetraspanin, was relatively specific to these cells. Through generating the first Tspan9 antibodies, Tspan9 expression was found to be tightly regulated in platelets. The relative levels of CD9, CD151, Tspan9 and CD63 were 100, 14, 6 and 2 respectively. Since CD9 was expressed at 49000 cell surface copies per platelet, this suggested a copy number of 2800 Tspan9 molecules. Finally, Tspan9 was shown to be a component of tetraspanin microdomains that included the collagen receptor GPVI (glycoprotein VI) and integrin α6β1, but not the von Willebrand receptor GPIbα or the integrins αIIbβ3 or α2β1. These findings suggest a role for Tspan9 in regulating platelet function in concert with other platelet tetraspanins and their associated proteins. |
format | Text |
id | pubmed-2652832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-26528322009-03-09 Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains Protty, Majd B. Watkins, Nicholas A. Colombo, Dario Thomas, Steven G. Heath, Victoria L. Herbert, John M. J. Bicknell, Roy Senis, Yotis A. Ashman, Leonie K. Berditchevski, Fedor Ouwehand, Willem H. Watson, Steve P. Tomlinson, Michael G. Biochem J Research Article Platelets are essential for wound healing and inflammatory processes, but can also play a deleterious role by causing heart attack and stroke. Normal platelet activation is dependent on tetraspanins, a superfamily of glycoproteins that function as ‘organisers’ of cell membranes by recruiting other receptors and signalling proteins into tetraspanin-enriched microdomains. However, our understanding of how tetraspanin microdomains regulate platelets is hindered by the fact that only four of the 33 mammalian tetraspanins have been identified in platelets. This is because of a lack of antibodies to most tetraspanins and difficulties in measuring mRNA, due to low levels in this anucleate cell. To identify potentially platelet-expressed tetraspanins, mRNA was measured in their nucleated progenitor cell, the megakaryocyte, using serial analysis of gene expression and DNA microarrays. Amongst 19 tetraspanins identified in megakaryocytes, Tspan9, a previously uncharacterized tetraspanin, was relatively specific to these cells. Through generating the first Tspan9 antibodies, Tspan9 expression was found to be tightly regulated in platelets. The relative levels of CD9, CD151, Tspan9 and CD63 were 100, 14, 6 and 2 respectively. Since CD9 was expressed at 49000 cell surface copies per platelet, this suggested a copy number of 2800 Tspan9 molecules. Finally, Tspan9 was shown to be a component of tetraspanin microdomains that included the collagen receptor GPVI (glycoprotein VI) and integrin α6β1, but not the von Willebrand receptor GPIbα or the integrins αIIbβ3 or α2β1. These findings suggest a role for Tspan9 in regulating platelet function in concert with other platelet tetraspanins and their associated proteins. Portland Press Ltd. 2008-12-12 2009-01-01 /pmc/articles/PMC2652832/ /pubmed/18795891 http://dx.doi.org/10.1042/BJ20081126 Text en © 2009 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Protty, Majd B. Watkins, Nicholas A. Colombo, Dario Thomas, Steven G. Heath, Victoria L. Herbert, John M. J. Bicknell, Roy Senis, Yotis A. Ashman, Leonie K. Berditchevski, Fedor Ouwehand, Willem H. Watson, Steve P. Tomlinson, Michael G. Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains |
title | Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains |
title_full | Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains |
title_fullStr | Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains |
title_full_unstemmed | Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains |
title_short | Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains |
title_sort | identification of tspan9 as a novel platelet tetraspanin and the collagen receptor gpvi as a component of tetraspanin microdomains |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652832/ https://www.ncbi.nlm.nih.gov/pubmed/18795891 http://dx.doi.org/10.1042/BJ20081126 |
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