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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...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2008
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.
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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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