Cytoplasmic regions of the β 3 subunit of integrin α IIbβ 3 involved in platelet adhesion on fibrinogen under flow conditions

Abstract

Platelet adhesion to surface-bound fibrinogen depends on integrin α IIbβ 3. In the present study, we investigated the role of the regions 749EATSTFT 756N and 755TNITYRG 762T of the β3 cytoplasmic tail in the regulation of platelet adhesion under flow conditions, by introducing peptide mimetics in platelets. Introduction of peptide EATSTFTN (E-N) increased surface coverage by 35%, an effect caused by 25% more adhesion. In contrast, peptide TNITYRGT (T-T) decreased surface coverage by 16%, as a result of 25% less adhesion. An S→P substitution in the E-N peptide, thereby mimicking a mutation in Glanzmann's thrombasthenia, abolished the effect of E-N. A suboptimal concentration of cytochalasin D is known to enhance ligand binding to α IIbβ 3 in platelet suspensions. Under flow, cytochalasin D (lμimol L -1) induced 50% more platelet adhesion, with a strong reduction in platelet spreading. Both peptides opposed the increase in adhesion by cytochalasin D and partly (E-N) and completely (T-T) restored platelet spreading. Thus, the 749EATSTFT 756N and 755TNITYRG 762T regions of β3 contribute to the regulation of odlbp3 anchorage to the cytoskeleton and platelet spreading to an adhesive surface. © 2003 International Society on Thrombosis and Haemostasis.