Cell 135, 334–342 (2008); Neuron 60, 285–297 (2008)

The connections between nerves and the muscles that enable animals to move and breathe cannot form without a protein called Agrin that activates an enzyme called MuSK. Two research groups have discovered that Agrin binds to Lrp4, a receptor, and together they switch on MuSK.

Steven Burden and a team from New York University Medical School stimulated normal and Lrp4-deficient developing muscle fibres with Agrin. MuSK was only activated in cells with Lrp4. The team then infected the mutant cells with a virus carrying the Lrp4 gene, which caused these cells to start producing the receptor. Agrin could then turn on MuSK.

Lin Mei, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his co-workers linked Lrp4 expression to the clustering of neurotransmitter receptors at the junction of nerve and muscle cells.