Thrombus formation begins when a few platelets settle down onto a sticky surface, such as collagens exposed during injury, or atherosclerotic plaques. The anchored platelets recruit other platelets through integrins and other adhesive proteins, forming a tight, clingy mass. This recruitment process depends on calcium oscillations that propagate from platelet to platelet, report W. Nesbitt et al. in the 31 March Journal of Cell Biology.

Credit: Reprinted with permission from JCB

In the top panel, a calcium spike surges through a platelet after exposure to von Willebrand factor, a sticky protein on the surface of platelets (high calcium levels are white, medium are red and low are blue). Such calcium spikes have been observed before in platelets settling down onto substrates in vessel walls. The bottom two panels illustrate the new findings: a new platelet, swept along as if in a vessel, contacts the anchored platelet at the peak of its calcium flux. This anchors the platelet and initiates a new calcium flux. Nesbitt et al. could induce such platelet attraction simply by activating calcium fluxes within individual platelets using a caged calcium chelator, triggered by exposure to ultraviolet light.

The investigators found that propagating the calcium spikes between platelets required αIIbβ3 integrin, a target of anti-clotting drugs. Also necessary was ADP, and an ADP receptor that may indirectly regulate calcium flux from internal stores. The authors suggest that integrin binding prompts calcium signaling, which in turn activates integrin and prompts ADP release. Calcium fluxes keep platelets sticky even under conditions of high shear flow, which occurs in the microcirculation and at sites of artery narrowing.