Aggregin: a platelet ADP receptor that mediates activation

Area of Science:

• Biochemistry
• Cell Biology
• Hematology

Background:

• Adenosine diphosphate (ADP) is a key mediator of platelet activation, inducing shape change, aggregation, and fibrinogen binding.
• Platelets possess a unique purinergic receptor that preferentially binds ADP over ATP.
• The 100 kDa membrane protein, aggregin, on the platelet surface is implicated in ADP-mediated responses.

Purpose of the Study:

• To identify and characterize the ADP receptor involved in platelet activation.
• To investigate the role of aggregin in ADP-induced platelet aggregation and fibrinogen binding.
• To elucidate the mechanism by which aggregin influences platelet function.

Main Methods:

• Utilized the affinity reagent 5'-p-fluorosulfonylbenzoyl adenosine (FSBA) to covalently label platelet membrane proteins.
• Assessed the effect of FSBA labeling on ADP-induced platelet shape change, aggregation, and fibrinogen binding.
• Compared the properties of aggregin with known platelet glycoproteins and receptors.

Main Results:

• FSBA covalently labeled a 100 kDa protein, aggregin, inhibiting ADP-induced platelet responses.
• Aggregin's properties differ from platelet glycoprotein IIIa and the adenylate cyclase-coupled receptor.
• Platelet aggregation induced by thromboxane A2 analogs, collagen, and epinephrine requires ADP binding to aggregin.
• Thrombin-induced aggregation involves calpain-mediated cleavage of aggregin, releasing fibrinogen receptor latency.

Conclusions:

• Aggregin functions as the primary ADP receptor mediating platelet shape change and aggregation.
• Aggregin plays a critical role in regulating fibrinogen receptor availability.
• ADP binding or proteolytic cleavage of aggregin is essential for relieving fibrinogen receptor latency.