SynCAMs

SynCAMs, or Synaptic Cell Adhesion Molecules, are a family of immunoglobulin superfamily proteins that promote the formation and maintenance of synapses in the nervous system. The family comprises four members, SynCAM1 through SynCAM4, encoded by the CADM1-4 genes. These type I transmembrane proteins mediate adhesive interactions across the synaptic cleft and contribute to synaptic density and organization.

Structurally, SynCAMs have an extracellular region with three Ig-like domains, a single transmembrane helix, and a cytoplasmic tail containing motifs that link to intracellular signaling and scaffolding networks. This architecture enables their adhesive function and coupling to intracellular pathways that influence cytoskeletal arrangement and synaptic components.

In neurons, SynCAMs are localized to both presynaptic and postsynaptic membranes and participate in homophilic trans interactions between axons and dendrites. Through these contacts, they promote synapse formation and can modulate synaptic density and architecture. Overexpression of SynCAMs in cultured neurons tends to increase synapse numbers, while disruption of their function can impair synaptogenesis, indicating a contributory role in synapse formation and maintenance. They are active in various CNS regions and can affect both excitatory and inhibitory synapses depending on neuronal context and developmental stage.

Intracellularly, the tails of SynCAMs interact with scaffolding and signaling proteins, connecting adhesive contacts to cytoskeletal organization and synaptic signaling pathways. Expression and activity of SynCAMs are developmentally regulated and responsive to neuronal activity.

Clinically, altered CADM gene expression has been linked to neurodevelopmental disorders in some studies, highlighting a potential role in synaptic plasticity and brain development. CADM1 is also studied as a tumor suppressor in certain cancers, illustrating diverse functions beyond the nervous system. SynCAMs were first described in the early 2000s, with evidence that they stimulate synapse formation in cultured neurons.