Title:
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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