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  Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions in mice

Klapproth, S., Moretti, F. A., Zeiler, M., Ruppert, R., Breithaupt, U., Mueller, S., et al. (2015). Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions in mice. BLOOD, 126(24), 2592-2600. doi:10.1182/blood-2015-04-639310.

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 Creators:
Klapproth, Sarah1, Author              
Moretti, Federico A.1, Author              
Zeiler, Marlis2, Author              
Ruppert, Raphael1, Author              
Breithaupt, Ute3, Author
Mueller, Susanna3, Author
Haas, Rainer3, Author
Mann, Matthias2, Author              
Sperandio, Markus3, Author
Fässler, Reinhard1, Author              
Moser, Markus1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
3external, ou_persistent22              

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Free keywords: HELICOBACTER-PYLORI INFECTION; INFLAMMATION IN-VIVO; INTEGRIN ACTIVATION; ADHESION DEFICIENCY; MOUSE; LFA-1; MAC-1; CELLS; AGGREGATION; RECRUITMENT
 Abstract: Hematopoietic cells depend on integrin-mediated adhesion and signaling, which is induced by kindlin-3 and talin-1. To determine whether platelet and polymorphonuclear neutrophil (PMN) functions require specific thresholds of kindlin-3, we generated mouse strains expressing 50%, 10%, or 5% of normal kindlin-3 levels. We report that in contrast to kindlin-3-null mice, which die perinatally of severe bleeding and leukocyte adhesion deficiency, mice expressing as little as 5% of kindlin-3 were viable and protected from spontaneous bleeding and infections. However, platelet adhesion and aggregation were reduced in vitro and bleeding times extended. Similarly, leukocyte adhesion, extravasation, and bacterial clearance were diminished. Quantification of protein copy numbers revealed stoichiometric quantities of kindlin-3 and talin-1 in platelets and neutrophils, indicating that reduction of kindlin-3 in our mouse strains progressively impairs the cooperation with talin-1. Our findings show that very low levels of kindlin-3 enable basal platelet and neutrophil functions, whereas in stress situations such as injury and infection, platelets and neutrophils require a maximum of functional integrins that is achieved with high and stoichiometric quantities of kindlin-3 and talin-1.

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Language(s): eng - English
 Dates: 2015
 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: 126 (24) Sequence Number: - Start / End Page: 2592 - 2600 Identifier: ISSN: 0006-4971