Agrin (green) is found at synaptic contacts as defined by synaptic vesicle localization (red).

At neuromuscular junctions, the extracellular matrix protein agrin directs the formation of postsynaptic structures. Agrin is also found in neurons of the central nervous system (CNS), so does it also direct synaptic development there? On page 923, Hoover et al. provide the first evidence of a specific agrin receptor involved in the development of synapses between two neurons.

The authors previously identified an agrin-induced signaling pathway in CNS neurons. The new work shows that the domain of agrin responsible for inducing this signal is within 20 kD of the carboxy terminus of the protein. A fragment from within this functional domain binds to the putative agrin receptor, but does not activate the signaling pathway, suggesting that receptor activation requires binding to two sites. Using the fragment as a probe reveals that agrin and its putative receptor colocalize at neuron–neuron synapses. The agrin receptor in the CNS is distinct from receptors that mediate agrin function at neuromuscular junctions.

The data suggest that agrin directs synaptic development or function in all neurons, regardless of their locations or neurotransmitter phenotypes. Hoover et al. are now trying to identify the agrin receptor in the CNS through affinity purification and expression library screening. ▪