HSPG 6-O sulfation (red) is missing from cells with QSulf1 (green).

The interactions of Wnt ligands with their receptors are helped by sulfated extracellular proteins called heparin sulfate proteoglycans (HSPGs). The sulfation state of HSPGs regulates activation of developmental signaling pathways, but it has not been clear how sulfation is controlled. A recently identified candidate, QSulf1, is transiently expressed in myogenic precursors and is required for Wnt-dependent expression of muscle specification genes. On page 341, Ai et al. demonstrate that QSulf1 is a unique sulfatase that remodels the cell surface to turn on Wnt signaling.

QSulf1 has a catalytic domain that resembles a lysosomal 6-O exosulfatase. But Ai and colleagues show that QSulf1 is a 6-O endosulfatase—the first enzyme shown to remove internal sulfates from disaccharides. Cells expressing QSulf1 had extensively different surface HSPGs that were highly desulfated compared with those on neighboring cells....

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