Cytoplasmic regions of the beta3 subunit of integrin alphaIIbbeta3 involved in platelet adhesion on fibrinogen under flow conditions.
Platelet adhesion to surface-bound fibrinogen depends on integrin alphaIIbbeta3. In the present study, we investigated the role of the regions 749EATSTFT756N and 755TNITYRG762T of the beta3 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 alphaIIbbeta3 in platelet suspensions. Under flow, cytochalasin D (1 micro mol 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 749EATSTFT756N and 755TNITYRG762T regions of beta3 contribute to the regulation of alphaIIbbeta3 anchorage to the cytoskeleton and platelet spreading to an adhesive surface.
Litjens
P E M H
PE
Laboratory for Thrombosis and Haemostasis, Department of Haematology, UMC Utrecht and Institute for Biomembranes, Utrecht University, Utrecht, the Netherlands. j.w.n.akkerman@lab.azu.nl
Kroner
C I
CI
Akkerman
J W N
JW
Van Willigen
G
G
D000595:Amino Acid Sequence / Q000502:physiology; D019943:Amino Acid Substitution; D015638:Cytochalasin D / Q000494:pharmacology; D003593:Cytoplasm; D003599:Cytoskeleton / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism / Q000502:physiology*; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*; D013915:Thrombasthenia / Q000235:genetics
D039661:Integrin beta3; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D015638:Cytochalasin D; D005340:Fibrinogen