Title:
Platelet glycoprotein Ibα forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF
Platelet glycoprotein Ibα forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF
dc.contributor.author | Yago, Tadayuki | en_US |
dc.contributor.author | Lou, Jizhong | en_US |
dc.contributor.author | Wu, Tao | en_US |
dc.contributor.author | Yang, Jun | en_US |
dc.contributor.author | Miner, Jonathan J. | en_US |
dc.contributor.author | Coburn, Leslie | en_US |
dc.contributor.author | López, José A. | en_US |
dc.contributor.author | Cruz, Miguel A. | en_US |
dc.contributor.author | Dong, Jing-Fei | en_US |
dc.contributor.author | McIntire,Larry V. | en_US |
dc.contributor.author | McEver, Rodger P. | en_US |
dc.contributor.author | Zhu, Cheng | en_US |
dc.contributor.corporatename | Oklahoma Medical Research Foundation. Cardiovascular Biology Research Program | en_US |
dc.contributor.corporatename | Georgia Institute of Technology. Dept. of Biomedical Engineering | en_US |
dc.contributor.corporatename | Emory University. Dept. of Biomedical Engineering | en_US |
dc.contributor.corporatename | Georgia Institute of Technology. Institute for Bioengineering and Bioscience | en_US |
dc.contributor.corporatename | University of Western Ontario. Mechanical and Materials Engineering Dept. | en_US |
dc.contributor.corporatename | Puget Sound Blood Center | en_US |
dc.contributor.corporatename | University of Washington, Seattle. Dept. of Medicine | en_US |
dc.contributor.corporatename | Baylor College of Medicine. Thrombosis Research Section | en_US |
dc.contributor.corporatename | University of Oklahoma Health Sciences Center. Dept. of Biochemistry and Molecular Biology | en_US |
dc.date.accessioned | 2013-06-03T20:16:36Z | |
dc.date.available | 2013-06-03T20:16:36Z | |
dc.date.issued | 2008-09 | |
dc.description | © 2008 The American Society for Clinical Investigation | en_US |
dc.description | The electronic version of this article is the complete one and can be found online at: http://www.jci.org/articles/view/35754 | en_US |
dc.description | DOI: 10.1172/JCI35754 | en_US |
dc.description.abstract | Arterial blood flow enhances glycoprotein Ibα (GPIbα) binding to vWF, which initiates platelet adhesion to injured vessels. Mutations in the vWF A1 domain that cause type 2B von Willebrand disease (vWD) reduce the flow requirement for adhesion. Here we show that increasing force on GPIbα/vWF bonds first prolonged (“catch”) and then shortened (“slip”) bond lifetimes. Two type 2B vWD A1 domain mutants, R1306Q and R1450E, converted catch bonds to slip bonds by prolonging bond lifetimes at low forces. Steered molecular dynamics simulations of GPIbα dissociating from the A1 domain suggested mechanisms for catch bonds and their conversion by the A1 domain mutations. Catch bonds caused platelets and GPIbα-coated microspheres to roll more slowly on WT vWF and WT A1 domains as flow increased from suboptimal levels, explaining flowenhanced rolling. Longer bond lifetimes at low forces eliminated the flow requirement for rolling on R1306Q and R1450E mutant A1 domains. Flowing platelets agglutinated with microspheres bearing R1306Q or R1450E mutant A1 domains, but not WT A1 domains. Therefore, catch bonds may prevent vWF multimers from agglutinating platelets. A disintegrin and metalloproteinase with a thrombospondin type 1 motif–13 (ADAMTS-13) reduced platelet agglutination with microspheres bearing a tridomain A1A2A3 vWF fragment with the R1450E mutation in a shear-dependent manner. We conclude that in type 2B vWD, prolonged lifetimes of vWF bonds with GPIbα on circulating platelets may allow ADAMTS-13 to deplete large vWF multimers, causing bleeding. | en_US |
dc.identifier.citation | Tadayuki Yago, Jizhong Lou, Tao Wu, Jun Yang, Jonathan J. Miner, Leslie Coburn, José A. López, Miguel A. Cruz, Jing-Fei Dong, Larry V. McIntire, Rodger P. McEver, and Cheng Zhu, “Platelet glycoprotein Ibα forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF,” Journal of Clinical Investigation, 118, 9, 3195-3207 (September 2008) | en_US |
dc.identifier.doi | 10.1172/JCI35754 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | http://hdl.handle.net/1853/47163 | |
dc.language.iso | en_US | en_US |
dc.publisher | Georgia Institute of Technology | en_US |
dc.publisher.original | American Society for Clinical Investigation | en_US |
dc.subject | Platelet adhesion | en_US |
dc.subject | Catch bonds | en_US |
dc.subject | von Willebrand disease | en_US |
dc.subject | Shear threshold | en_US |
dc.title | Platelet glycoprotein Ibα forms catch bonds with human WT vWF but not with type 2B von Willebrand disease vWF | en_US |
dc.type | Text | |
dc.type.genre | Article | |
dspace.entity.type | Publication | |
local.contributor.author | Zhu, Cheng | |
local.contributor.corporatename | Wallace H. Coulter Department of Biomedical Engineering | |
local.contributor.corporatename | College of Engineering | |
relation.isAuthorOfPublication | d28f1a84-f07d-40ec-bed3-60bc4c140551 | |
relation.isOrgUnitOfPublication | da59be3c-3d0a-41da-91b9-ebe2ecc83b66 | |
relation.isOrgUnitOfPublication | 7c022d60-21d5-497c-b552-95e489a06569 |
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