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  Direct Rap1/Talin1 interaction regulates platelet and neutrophil integrin activity in mice

Bromberger, T., Klapproth, S., Rohwedder, I., Zhu, L., Mittmann, L., Reichel, C. A., et al. (2018). Direct Rap1/Talin1 interaction regulates platelet and neutrophil integrin activity in mice. Blood, 132(26), 2754-2762. doi:10.1182/blood-2018-04-846766.

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Genre: Journal Article

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 Creators:
Bromberger, Thomas1, Author              
Klapproth, Sarah1, Author              
Rohwedder, Ina2, Author
Zhu, Liang2, Author
Mittmann, Laura2, Author
Reichel, Christoph A.2, Author
Sperandio, Markus2, Author
Qin, Jun2, 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: LEUKOCYTE ADHESION DEFICIENCY; EFFECTOR RIAM; TALIN; RAP1; DOMAIN; ACTIVATION; SECRETION; BINDINGHematology;
 Abstract: Targeting Talin1 to the plasma membrane is a crucial step in integrin activation, which in leukocytes is mediated by a Rap1/RIAM/Talin1 pathway, whereas in platelets, it is RIAM independent. Recent structural, biochemical, and cell biological studies have suggested direct Rap1/Talin1 interaction as an alternative mechanism to recruit Talin1 to the membrane and induce integrin activation. To test whether this pathway is of relevance in vivo, we generated Rap1 binding-deficient Talin1 knockin (Tln1(3mut)) mice. Although Tln1(3mut) mice showed no obvious abnormalities, their platelets exhibited reduced integrin activation, aggregation, adhesion, and spreading, resulting in prolonged tail-bleeding times and delayed thrombus formation and vessel occlusion in vivo. Surprisingly, neutrophil adhesion to different integrin ligands and beta 2 integrin-dependent phagocytosis were also significantly impaired, which caused profound leukocyte adhesion and extravasation defects in Tln1(3mut) mice. In contrast, macrophages exhibited no defect in adhesion or spreading despite reduced integrin activation. Taken together, our findings suggest that direct Rap1/Talin1 interaction is of particular importance in regulating the activity of different integrin classes expressed on platelets and neutrophils, which both depend on fast and dynamic integrin-mediated responses.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Blood
  Other : Blood
Source Genre: Journal
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Publ. Info: Philadelphia, Pa. : W.B. Saunders
Pages: - Volume / Issue: 132 (26) Sequence Number: - Start / End Page: 2754 - 2762 Identifier: ISSN: 0006-4971
CoNE: https://pure.mpg.de/cone/journals/resource/954925385125