Linked Life Data

21156842

Source:http://linkedlifedata.com/resource/pubmed/id/21156842

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2011-3-4
pubmed:abstractText
Platelets have evolved a highly specialized membrane skeleton that provides stability to the plasma membrane and facilitates adhesion under high shear stress. The cytoskeletal anchorage of glycoprotein (GP) Ib? plays an important role in regulating the membrane skeleton. However, its role in regulating membrane stability remains unknown. To investigate this role, we have developed a new mouse model that expresses wild-type human GPIb? (hGPIb?(WT)), or a mutant form of human GPIb? that has a selective defect in its ability to bind filamin A and anchor to the membrane skeleton (hGPIb?(FW)-Phe568Ala and Trp570Ala substitutions). Our study demonstrates that the link between platelet GPIb and the cytoskeleton does not alter the intrinsic ligand binding function of GPIb? or the ability of the receptor to stimulate integrin ?(IIb)?(3)-dependent spreading. However, exposure of hGPIb?(FW) platelets to pathologic shear rate levels (5000 to 40,000 s(-1)) leads to the development of unstable membrane tethers, defective platelet adhesion, and loss of membrane integrity, leading to complete disintegration of the platelet cell body. These outcomes suggest that the GPIb?-filamin A interaction not only regulates the architecture of the membrane skeleton, but also maintains the mechanical stability of the plasma membrane under conditions of high shear.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1528-0020
pubmed:author
pubmed:copyrightInfo
© 2011 by The American Society of Hematology
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2718-27
pubmed:dateRevised
2011-10-11
pubmed:meshHeading
pubmed-meshheading:21156842-Animals, pubmed-meshheading:21156842-Blood Platelets, pubmed-meshheading:21156842-Caspases, pubmed-meshheading:21156842-Cell Membrane, pubmed-meshheading:21156842-Cell Movement, pubmed-meshheading:21156842-Contractile Proteins, pubmed-meshheading:21156842-Cytoskeletal Proteins, pubmed-meshheading:21156842-Humans, pubmed-meshheading:21156842-Immobilized Proteins, pubmed-meshheading:21156842-Mice, pubmed-meshheading:21156842-Mice, Transgenic, pubmed-meshheading:21156842-Microfilament Proteins, pubmed-meshheading:21156842-Models, Animal, pubmed-meshheading:21156842-Mutant Proteins, pubmed-meshheading:21156842-Platelet Adhesiveness, pubmed-meshheading:21156842-Platelet Glycoprotein GPIb-IX Complex, pubmed-meshheading:21156842-Protein Binding, pubmed-meshheading:21156842-Stress, Mechanical, pubmed-meshheading:21156842-von Willebrand Factor
pubmed:year
2011
pubmed:articleTitle
High shear-dependent loss of membrane integrity and defective platelet adhesion following disruption of the GPIb?-filamin interaction.
pubmed:affiliation
Australian Centre for Blood Diseases, Monash University, Alfred Medical Research & Education Precinct, Melbourne, Victoria 3004, Australia. sue.cranmer@monash.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't