Seven-protein complex initiates clotting

A seven-protein complex drives blood clotting by initiating actin polymerization in platelets.

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Actin polymerization results in the sequential formation of filopodia, lamellipodia, and stress fibers in platelets, but the molecular mechanisms regulating these processes were unknown. In 15 June Blood, Zhi Li and colleagues at Brown University, Rhode Island, US show that the Arp2/3 complex nucleates actin polymerization in vitro (Blood 2002, 99:4466-4474).

Li et al. developed a new method to permeabilize resting platelets, while preserving their ability to adhere and form filopodia and lamellipodia on exposure to glass. Arp2-specific antibodies were then added, which prevented thrombin receptor activation of actin polymerization by the thrombin receptor activating peptide (TRAP).

Antibody treatment froze the platelets at the rounded, early stage of activation, before the formation of filopodia or lamellipodia. Analysis indicated that the proportion of platelets at the rounded stage rose from 2.85% before treatment to 63% afterwards. Addition of a recombinant Arp2 protein reversed this effect.

They hope that their identification of ...

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