Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor
Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIba subunit of GPIb-IX was identified. He...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
Macmillan Publishers Limited
2016
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| Online Access: | http://hdl.handle.net/20.500.11937/54969 |
| _version_ | 1848759510976430080 |
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| author | Deng, W. Xu, Y. Chen, W. Paul, D. Syed, A. Dragovich, M. Liang, X. Zakas, P. Berndt, Michael Di Paola, J. Ware, J. Lanza, F. Doering, C. Bergmeier, W. Zhang, X. Li, R. |
| author_facet | Deng, W. Xu, Y. Chen, W. Paul, D. Syed, A. Dragovich, M. Liang, X. Zakas, P. Berndt, Michael Di Paola, J. Ware, J. Lanza, F. Doering, C. Bergmeier, W. Zhang, X. Li, R. |
| author_sort | Deng, W. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIba subunit of GPIb-IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane € Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb-IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors. |
| first_indexed | 2025-11-14T10:01:02Z |
| format | Journal Article |
| id | curtin-20.500.11937-54969 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:01:02Z |
| publishDate | 2016 |
| publisher | Macmillan Publishers Limited |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-549692017-11-07T08:51:45Z Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor Deng, W. Xu, Y. Chen, W. Paul, D. Syed, A. Dragovich, M. Liang, X. Zakas, P. Berndt, Michael Di Paola, J. Ware, J. Lanza, F. Doering, C. Bergmeier, W. Zhang, X. Li, R. Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib-IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIba subunit of GPIb-IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane € Trigger' sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb-IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors. 2016 Journal Article http://hdl.handle.net/20.500.11937/54969 10.1038/ncomms12863 http://creativecommons.org/licenses/by/4.0/ Macmillan Publishers Limited fulltext |
| spellingShingle | Deng, W. Xu, Y. Chen, W. Paul, D. Syed, A. Dragovich, M. Liang, X. Zakas, P. Berndt, Michael Di Paola, J. Ware, J. Lanza, F. Doering, C. Bergmeier, W. Zhang, X. Li, R. Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| title | Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| title_full | Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| title_fullStr | Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| title_full_unstemmed | Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| title_short | Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| title_sort | platelet clearance via shear-induced unfolding of a membrane mechanoreceptor |
| url | http://hdl.handle.net/20.500.11937/54969 |