Agrin treatment (right) pulls acetylcholine receptors (white) into action.

The nerve-derived growth factor agrin is now shown by Martin et al. (page 503) to turn broadcast communication into personalized messaging.Agrin is well-established as a differentiation and maturation factor at the neuromuscular junction: it helps form the connections between nerves and muscles by inducing aggregation of acetylcholine receptors on muscle cells. Now, Martin et al. demonstrate that agrin also promotes synaptogenesis between two neurons. The protein shuts off gap junction-mediated communication between cells while stimulating maturation of the nicotinic synapses.

Agrin is widely expressed in neural tissue, including the adrenal gland, but its function there wasn't clear. Meanwhile, intercellular connections between chromaffin cells in the developing adrenal medulla shift during the first week after birth from electrically modulated communication using gap junctions to synaptic communication that is chemically based. The factors that control that shift have also been obscure.

When Martin et al. added agrin to slices of immature adrenal tissue from neonate rats, the gap junction channels closed within several minutes, limiting dye and ion movement. Within an hour of exposure to agrin, the size of spontaneous excitatory postsynaptic nicotinic currents detected in these cells increased substantially. Although both changes were induced by agrin, inhibition of one change did not affect the other, indicating that they were independent of each other. Inhibition of Src signaling blocked both changes, consistent with the known expression of Src in adrenal chromaffin cells and its use by agrin at the neuromuscular junction.

Increasing evidence indicates that gap junction activity and synaptic communication are antagonistic during synaptogenesis. With agrin's broad expression in the developing CNS, the proteoglycan may help coordinate the shift from one type of communication to another throughout the nervous system.