A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin ?(2) ?(1).
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ABSTRACT: BACKGROUND:Collagen-induced platelet activation is a key step in the development of arterial thrombosis via its interaction with the receptors glycoprotein (GP)VI and integrin ?(2) ?(1) . Adhesion and degranulation-promoting adapter protein (ADAP) regulates ?(IIb) ?(3) in platelets and ?(L) ?(2) in T cells, and is phosphorylated in GPVI-deficient platelets activated by collagen. OBJECTIVES:To determine whether ADAP plays a role in collagen-induced platelet activation and in the regulation and function of ?(2) ?(1). METHODS:Using ADAP(-/-) mice and synthetic collagen peptides, we investigated the role of ADAP in platelet aggregation, adhesion, spreading, thromboxane synthesis, and tyrosine phosphorylation. RESULTS AND CONCLUSIONS:Platelet aggregation and phosphorylation of phospholipase C?2 induced by collagen were attenuated in ADAP(-/-) platelets. However, aggregation and signaling induced by collagen-related peptide (CRP), a GPVI-selective agonist, were largely unaffected. Platelet adhesion to CRP was also unaffected by ADAP deficiency. Adhesion to the ?(2) ?(1) -selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and ?(2) ?(1), was reduced in ADAP(-/-) platelets. An impedance-based label-free detection technique, which measures adhesion and spreading of platelets, indicated that, in the absence of ADAP, spreading on GFOGER was also reduced. This was confirmed with non-fluorescent differential-interference contrast microscopy, which revealed reduced filpodia formation in ADAP(-/-) platelets adherent to GFOGER. This indicates that ADAP plays a role in mediating platelet activation via the collagen-binding integrin ?(2) ?(1). In addition, we found that ADAP(-/-) mice, which are mildly thrombocytopenic, have enlarged spleens as compared with wild-type animals. This may reflect increased removal of platelets from the circulation.
SUBMITTER: Jarvis GE
PROVIDER: S-EPMC3791415 | biostudies-literature | 2012 Feb
REPOSITORIES: biostudies-literature
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