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  beta 1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse

Petzold, T., Ruppert, R., Pandey, D., Barocke, V., Meyer, H., Lorenz, M., et al. (2013). beta 1 integrin-mediated signals are required for platelet granule secretion and hemostasis in mouse. BLOOD, 122(15), 2723-2731. doi:10.1182/blood-2013-06-508721.

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 Creators:
Petzold, Tobias1, Author              
Ruppert, Raphael1, Author              
Pandey, Dharmendra1, Author              
Barocke, Verena2, Author
Meyer, Hannelore1, Author              
Lorenz, Michael2, Author
Zhang, Lin2, Author
Siess, Wolfgang2, Author
Massberg, Steffen2, Author
Moser, Markus1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2external, ou_persistent22              

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Free keywords: GLYCOPROTEIN-VI; IN-VIVO; ALPHA-GRANULE; COLLAGEN; ALPHA(2)BETA(1); ACTIVATION; ADHESION; RECEPTOR; KINASE; AGGREGATION
 Abstract: Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific aIIbb3 integrin is known to be crucial for these processes, the in vivo role of beta 1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of beta 1 integrins or an activationdeficient beta 1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of beta 1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of beta 1 integrins are able to trigger intracellular signals driving Rac-12 dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet beta 1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote beta 1 integrins as a promising and so far clinically unemployed antithrombotic target.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: BLOOD
Source Genre: Journal
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Publ. Info: 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA : AMER SOC HEMATOLOGY
Pages: - Volume / Issue: 122 (15) Sequence Number: - Start / End Page: 2723 - 2731 Identifier: ISSN: 0006-4971