Control of blood clotting by platelets described; provides medical promise

Nov 24, 2009

Cell fragments called platelets are essential to promote blood clotting. Virginia Tech faculty members and students have discovered novel molecular interactions at the surface of platelets that control blood clotting.

The Virginia Tech researchers describe how platelets perform this life-saving magic in the November 24 online issue of the journal PLoS ONE (Public Library of Science) in the article "Sulfatides Partition Disabled-2 in Response to Platelet Activation," by Karen E. Drahos, biological sciences Master's degree student from Roanoke, Va.; John D. Welsh, a biological sciences undergraduate student from Pennington, N.J.; and biological sciences Assistant Professors Carla V. Finkielstein and Daniel G. S. Capelluto.

Capelluto and Finkielstein study how proteins signal from biological membranes. One such membrane protein is the integrin receptor that resides on the surface of platelets. A protein that strongly promotes platelet activation through the integrin receptor is thrombin. When there is tissue injury, thrombin converts fibrinogen into fibrin to form a network that traps and platelets, creating a clot.

However, the platelets may not remain trapped. They can break their bonds with the network and thin or remove a clot - a good thing if the clot is blocking an artery, as in or stroke.

One part of the process is well known. When a platelet is stimulated, such as by thrombin, the protein Disabled-2 (Dab2) moves from where it is stored inside of the platelet to the surface, where it interacts with the integrin receptor. If this is the case, Dab2 inhibits .

Experimentation and measurements by the Virginia Tech researchers revealed that Dab2 also binds to sulfatides, a that also resides on the surface of platelets. Sulfatides sequester Dab2 proteins, preventing them from binding to the integrin receptor.

"That is, sulfatides partition Dab2 into two pools - one pool that is part of the clotting process and one pool that prevents coagulation," said Capelluto.

When no longer on high alert to regulate clotting, the Dab2 proteins return to the interior of the platelet. "They are likely recycled for the next time they are needed," said Capelluto.

The study was Drahos' Master's thesis research, conducted in both Capelluto's and Finkielstein's labs. The thesis received the 2009 William Preston Society Thesis Award in Life Sciences for the best original research with potential to benefit all people. Co-author John Welsh is now a graduate student in Finkielstein's lab.

The article stops with the definition of the chemistry of platelets' two responses to thrombin. But research by Finkielstein and Capelluto is looking at the platelet aggregation inhibitor process as a target for intervention to control bleeding and clotting. "This promises a high impact at the clinical level," said Capelluto. "The goal is a tool that could be used in surgery and could help people with bleeding or blood clotting disorders without drugs and side effects."

Source: Virginia Tech (news : web)

Explore further: Scientists 1 step closer to cell therapy for multiple sclerosis patients

add to favorites email to friend print save as pdf

Related Stories

How life-threatening blood clots take hold

Apr 16, 2009

When plaques coating blood vessel walls rupture and expose collagen, platelets spring into action to form a blood clot at the damaged site. Now, a new report in the April 17th issue of the journal Cell, a Cell Press public ...

New clot-buster found

Jan 20, 2009

(PhysOrg.com) -- Exciting research into blood clotting by British Heart Foundation (BHF) researchers working at the University of Bristol will take us a step closer to better heart attack prevention and treatment. ...

Key found to breakthrough drug for clot victims

Mar 10, 2008

A team of researchers at Oregon Health & Science University and Washington University in St. Louis have described for the first time the mechanism that gives a mutant enzyme molecule that they have engineered – and patented ...

A novel target for therapeutics against Staph infection

Nov 28, 2008

Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology, and the University of Edinburgh have uncovered how a bacterial pathogen interacts with the blood coagulation protein fibrinogen to ...

Study points to potential new use for Viagra

Aug 26, 2008

A "basic science" breakthrough by Queen's University researchers into regulating a single enzyme may lead to new drug therapies that will help prevent heart attacks and strokes.

Recommended for you

Monitoring the rise and fall of the microbiome

54 minutes ago

Trillions of bacteria live in each person's digestive tract. Scientists believe that some of these bacteria help digest food and stave off harmful infections, but their role in human health is not well understood.

Antioxidant biomaterial promotes healing

8 hours ago

When a foreign material like a medical device or surgical implant is put inside the human body, the body always responds. According to Northwestern University's Guillermo Ameer, most of the time, that response can be negative ...

Immune response may cause harm in brain injuries, disorders

10 hours ago

Could the body's own immune system play a role in memory impairment and cognitive dysfunction associated with conditions like chronic epilepsy, Alzheimer's dementia and concussions? Cleveland Clinic researchers believe so, ...

User comments : 0