VWF springs into action

Following blood vessel injury, long strings of multimeric von Willebrand's factor (VWF) act as a scaffold for platelets to help staunch bleeding. The VWF strings, 100-μm long or more, may be stored as a coiled, tubular spring inside obligately extended organelles, suggest Grégoire Michaux, Daniel Cutler (University College London, UK), and colleagues.

These organelles are the 1–5 μm-long Weibel-Palade bodies (WPBs). “If you look down a microscope they are such striking organelles—long and just very pretty,” says Cutler. “There had to be something underlying this.”

Cutler's answer was striking. “The shape is determined by the function of the protein after exocytosis,” he says. The organelle needs to be long, he suggests, so that the spring can be stored in a straight line, allowing easy expansion upon release. “If it is coiled [inside the cell],” he says, “100-fold compaction is reasonable.”

The compaction is dependent on the pro-region of VWF. After cleavage in the Golgi, it stays glued to VWF until the two hit the bloodstream. When the pH changes from acidic (inside the organelle) to near-neutral (in the blood), the pro-region is released and VWF unfurls into the bloodstream.

When the UK team used drugs to neutralize the pH inside WPBs earlier, the tubular nature of VWF was lost, the organelles rounded up, and any VWF subsequently released from the cell formed short and sometimes tangled filaments. This correlation of form and later function prompted the model. Structural studies will be needed to confirm the details.

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