NCAM anchors TGN organelles (red) at contact sites.

In the central nervous system, synapses form when specific organelles and proteins are recruited to a site where the axon of one cell contacts a dendrite of another. But how do the cells coordinate the extracellular formation of a contact with the intracellular movement of organelles? On page 649, Sytnyk et al. describe the interaction of neural cell adhesion molecule (NCAM) clusters with intracellular organelle aggregates derived from the trans-Golgi network (TGN). The work is the first demonstration that recognition molecules such as NCAM directly link extracellular signals to intracellular organelle movement at developing synapses.

As NCAM was believed to stabilize the contact structure in synaptogenesis, the authors examined the movements and localization of NCAM and the TGN organelles in cultured hippocampal neurons. The results show that spectrin links the TGN organelles directly to clusters of NCAM, and that NCAM is one of the first proteins to accumulate at sites where neurites contact each other. The trapping of NCAM and its associated organelles at contact sites is followed by the development of the contacts into functional synapses.

NCAM appears to be attached to TGN organelles before entering the contact site. This suggests a model in which intracellular motor proteins move the TGN organelles along the intracellular sides of the neurites, pulling NCAM across the extracellular surface of the membrane at the same time. At a developing contact site, the NCAM molecules of the two cells cluster, trapping the TGN organelles and stabilizing the nascent synapse.

At later developmental stages in hippocampal cultures, NCAM is responsible for stabilization only on the postsynaptic sides of synapses, suggesting that it may serve additional functions once the synapse has formed. Previous work has already shown that NCAM is required for the proper mobilization and cycling of synaptic vesicles at neuromuscular junctions. ▪