VWF springs into action

The Geneva group had earlier found factors linking transcription activation to the nuclear pore. They now use a nuclease fused to a nuclear pore protein, which clips any DNA that comes to the nuclear pore for a visit. The regions preferentially cleaved by the nuclease were just upstream of 40% of genes on chromosome VI. Constitutively expressed genes use different promoter elements and may not need the activation conferred by the visit. But back-of-the-envelope calculations suggest that there are enough pores for all activated genes to get in a quick visit, even if they do so for every round of transcription. Laemmli suggests that “the pore is an active participant in forming a complex between enhancer and promoter.” Constrained enhancers could no longer infl uence more distant promoters. In higher eukaryotes, Laemmli thinks that so-called transcription factories may act as promoter attachment and assembly sites, and thus as the intranuclear equivalent of nuclear pores. In yeast, the Geneva group is mutating a newly isolated gene that should confi rm whether the visit to the pore is an essential event. Reference: Schmid, M., et al. 2005. Mol. Cell. 21:379–391. F ollowing 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 fi laments. This correlation of form and later function prompted the model. Structural studies will be needed to confi rm the details. Reference: Michaux, G., et al. 2005. Dev. Cell. 10:223–232.