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UNC Scientists Discover 'Gatekeeper' Protein In Blood Clotting

Date:
January 26, 2006
Source:
University of North Carolina School of Medicine
Summary:
New research from the University of North Carolina at Chapel Hill School of Medicine has identified a protein that may control blood clotting by keeping blood platelets from sticking together.

New research from the University of North Carolina at Chapel Hill School of Medicine has identified a protein that may control blood clotting by keeping blood platelets from sticking together.

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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.

"Our data suggest that CIB1 may be one of the body's own natural anti-coagulants -- as long as CIB1 is bound to GPIIb/IIIa, the platelet stays quiet. However, if a person doesn't have enough CIB1 or their CIB1 isn't functional, then their platelets may have the potential to be hyper-responsive and pathologically predisposed to clotting," Parise said. Additionally, the authors propose that CIB1 maintains the adhesion receptor in its inactive state by preventing the binding of another protein called talin to GPIIb/IIIa, which has been shown in other studies to be an adhesion receptor activator.

"CIB1 and talin compete for binding to the adhesion receptor; therefore, we think that as long as CIB1 is bound to the adhesion receptor, this prevents talin from binding and activating the receptor," said Dr. Tina Leisner, assistant professor of pharmacology and one of the study's primary authors.

The group now plans further study of the molecular mechanisms of the CIB1/GPIIb/IIIa interaction, which could lead to the development of new therapies in the prevention of platelet activation.

###

Along with Parise, Yuan and Leisner, co-authors on the study include Parise lab members Andrew W. McFadden, Dr. Zhengyan Wang, Shantres Clark, Dr. Christel Boudignon-Proudhon and Dr. Mark K. Larson. Stephen C.-T. Lam of the University of Illinois at Chicago's department of pharmacology also co-authored the study.

This work was supported by grants from the National Institutes of Health.



Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of North Carolina School of Medicine. "UNC Scientists Discover 'Gatekeeper' Protein In Blood Clotting." ScienceDaily. ScienceDaily, 26 January 2006. <www.sciencedaily.com/releases/2006/01/060126190116.htm>.
University of North Carolina School of Medicine. (2006, January 26). UNC Scientists Discover 'Gatekeeper' Protein In Blood Clotting. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2006/01/060126190116.htm
University of North Carolina School of Medicine. "UNC Scientists Discover 'Gatekeeper' Protein In Blood Clotting." ScienceDaily. www.sciencedaily.com/releases/2006/01/060126190116.htm (accessed October 24, 2014).

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