Uncontrolled interactions between blood platelets such as those that occur during heart attacks and strokes contribute to these leading causes of death nationwide.
The study, which appears in the Jan. 17 edition of the Journal of Cell Biology, indicates that CIB1 binds to and keeps the platelet adhesion receptor GPIIb/IIIa in an inactive state, thus blocking platelet-to-platelet interactions in the blood.
Dr. Weiping Yuan, an assistant professor in UNC's department of pharmacology and the study's lead author, said CIB1's role was as a "gatekeeper" of GPIIb/IIIa activation. "Originally, I was a little surprised. We expected CIB1 itself to activate GPIIb/IIIa, but that is clearly not the case. CIB1 keeps GPIIb/IIIa turned off until it should be activated."
The UNC laboratory of Dr. Leslie V. Parise, professor of pharmacology and the new study's senior author, discovered the protein CIB1 in 1997. It was found inside platelets as a protein that binds to GPIIb/IIIa.
Under normal conditions, GPIIb/IIIa, found on the surface of platelets, remains in a resting, inactive state that allows normal blood flow. However, during clotting, GPIIb/IIIa becomes active, binds platelets to one another and attaches them to the blood vessel wall, thus forming a clot.
GPIIb/IIIa also is the target of several anti-coagulation drug therapies used in the clinic today, but the study suggests that knowledge of how CIB1 functions may lead to new therapeutic approaches.
The report, which used platelet precursor cells, demonstrated that decreasing the amount of CIB1 in these cells makes GPIIb/IIIa more responsive, thus more likely to mediate blood clotting. Increasing the amount of CIB1 prevented GPIIb/IIIa activation.