Pre- and postsynaptic actions of L1-CAM in nicotinic pathways

Cell adhesion molecules (CAMs) have long been known to guide axon outgrowth and pathfinding. More recent evidence indicates they contribute to synapse formation as well. The L1 family of IgCAMs has been implicated in long-term potentiation, learning, and some features of synaptic structure. We show here that L1 is localized in nicotinic pathways at both pre- and postsynaptic sites. In the chick ciliary ganglion, postsynaptic L1 is associated with nicotinic receptors and potentiates their downstream signaling. Postsynaptic L1 is also important for aligning presynaptic structures over the postsynaptic cell. Dominant negative experiments suggest this latter effect depends on homophilic interactions with presynaptic L1. At the neuromuscular junction L1 is also found presynaptically where dominant negative experiments again indicate a role in aligning presynaptic structures over postsynaptic receptors, both in culture and in vivo. These findings identify new roles for L1 at nicotinic synapses and underscore the multipotency of L1-CAMs.