A role for adhesion and degranulation-promoting adapter protein in collagen-induced platelet activation mediated via integrin α(2) β(1)

J Thromb Haemost. 2012 Feb;10(2):268-77. doi: 10.1111/j.1538-7836.2011.04567.x.


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 α(2) β(1) . Adhesion and degranulation-promoting adapter protein (ADAP) regulates α(IIb) β(3) in platelets and α(L) β(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 α(2) β(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 Cγ2 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 α(2) β(1) -selective ligand GFOGER and to a peptide (III-04), which supports adhesion that is dependent on both GPVI and α(2) β(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 α(2) β(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Blood Platelets / metabolism*
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism
  • Carrier Proteins / metabolism
  • Collagen / metabolism*
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / metabolism
  • Integrin alpha2beta1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptides / metabolism
  • Phospholipase C gamma / metabolism
  • Phosphorylation
  • Platelet Activation*
  • Platelet Adhesiveness
  • Platelet Aggregation
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Pseudopodia / metabolism
  • Splenomegaly / genetics
  • Splenomegaly / metabolism
  • Thrombocytopenia / genetics
  • Thrombocytopenia / metabolism
  • Thromboxane A2 / metabolism
  • Thromboxane B2 / metabolism
  • Time Factors
  • Tyrosine


  • Adaptor Proteins, Signal Transducing
  • CD36 Antigens
  • Carrier Proteins
  • Fyb protein, mouse
  • Immunoglobulin Variable Region
  • Integrin alpha2beta1
  • Peptides
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • collagen-related peptide
  • Tyrosine
  • Thromboxane B2
  • Thromboxane A2
  • Collagen
  • Phospholipase C gamma