Characterization of mice with a platelet-specific deletion of the adapter molecule ADAP.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsRudolph, Jochen Michael
Meinke, Clara Antonia
MetadataShow full item record
AbstractThe adhesion and degranulation-promoting adapter protein (ADAP) is expressed in T cells, NK cells, myeloid cells, and platelets. The involvement of ADAP in the regulation of receptor-mediated inside-out signaling leading to integrin activation is well characterized, especially in T cells and in platelets. Due to the fact that animal studies using conventional knock-out mice are limited by the overlapping effects of the different ADAP-expressing cells, we generated conditional ADAP knock-out mice (ADAPfl/fl PF4-Cretg). We observed that loss of ADAP restricted to the megakaryocytic lineage has no impact on other hematopoietic cells even after stimulation conditions. ADAPfl/fl PF4-Cretg mice showed thrombocytopenia in combination with reduced plasma levels of PF4 and TGF-β1. In vitro, platelets from these mice revealed reduced P-selectin expression, lower TGF-β1 release, diminished integrin αIIbβ3 activation and decreased fibrinogen binding after stimulation with podoplanin, the ligand of the C-type lectin-like receptor-2 (CLEC-2). Furthermore, loss of ADAP was associated with impaired CLEC-2-mediated activation of PLCγ2 and Erk1/2. Induction of experimental autoimmune encephalomyelitis (EAE) in mice lacking ADAP expression in platelets caused a more severe disease. In vivo administration of TGF-β1 early after T cell transfer improved EAE severity in mice with loss of ADAP restricted to platelets. Our results reveal a regulatory function of ADAP in platelets in vitro and during autoimmune disease EAE in vivo.
AffiliationHZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany.
JournalMolecular and Cellular Biology
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Immune Cell-Type Specific Ablation of Adapter Protein ADAP Differentially Modulates EAE.
- Authors: Rudolph J, Meinke C, Voss M, Guttek K, Kliche S, Reinhold D, Schraven B, Reinhold A
- Issue date: 2019
- A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1).
- Authors: Jarvis GE, Bihan D, Hamaia S, Pugh N, Ghevaert CJ, Pearce AC, Hughes CE, Watson SP, Ware J, Rudd CE, Farndale RW
- Issue date: 2012 Feb
- ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding.
- Authors: Kasirer-Friede A, Kang J, Kahner B, Ye F, Ginsberg MH, Shattil SJ
- Issue date: 2014 May 15
- T cell-independent modulation of experimental autoimmune encephalomyelitis in ADAP-deficient mice.
- Authors: Engelmann S, Togni M, Thielitz A, Reichardt P, Kliche S, Reinhold D, Schraven B, Reinhold A
- Issue date: 2013 Nov 15
- ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia.
- Authors: Spindler M, van Eeuwijk JMM, Schurr Y, Nurden P, Nieswandt B, Stegner D, Reinhold A, Bender M
- Issue date: 2018 Aug 9