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New research links αIIbβ3 to Glanzmann thrombasthenia
Apr 20, 2006, 17:02, Reviewed by: Dr. Priya Saxena
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Together, the two proteins � αIIb and β3 � create a cellular receptor that�s involved in aggregating blood cells for coagulation; analyzing patients with the disorder previously led Coller to develop a novel therapy for heart-attack and stroke victims that targets this receptor.
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By Rockefeller University,
Studying receptors on the surface of blood platelets, sticky cells that cause blood to clot, has given one Rockefeller researcher new insight into potential causes and treatments for certain cardiovascular diseases. Barry Coller, David Rockefeller Professor and the university�s physician-in-chief, has been focusing on a rare disorder known as Glanzmann thrombasthenia, in which platelets lack one of two proteins. Together, the two proteins � αIIb and β3 � create a cellular receptor that�s involved in aggregating blood cells for coagulation; analyzing patients with the disorder previously led Coller to develop a novel therapy for heart-attack and stroke victims that targets this receptor.
In research published in the April 1 issue of Blood, Coller and Beau Mitchell, a research associate in Coller�s lab, further characterize the αIIbβ3 receptor by exploring its production and degradation. With colleagues at the Mount Sinai School of Medicine, they found that the production of the receptor, the protein complex of both αIIb and β3, is dependent on a third molecule called calnexin. Calnexin plays an important role in protein folding, and the researchers found that it not only helps form the αIIbβ3 receptor complex, but also tags improperly folded β3 proteins for destruction. Their findings suggest that the factor that controls receptor formation is likely the calnexin cycle; if the two receptor proteins fail to form a correctly folded complex, αIIb is broken down by the cell. Coller hopes that further study of αIIbβ3 will yield more information about not just Glanzmann thrombasthenia but the synthesis of other receptors like it. These receptors, which are in the integrin superfamily, play a role in many different functions, including embryonic development, inflammation, and tumor growth and metastases, Coller says. �Insights into rare diseases allow us to study and devise strategies for common diseases.� 
- April 1 issue of Blood
Blood 107(7): 2713-2719 (April 1, 2006)
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