SynCAMs were first identified as calcium-independent synapse-inducing molecules but are also known to mediate myelination by facilitating the interaction between Schwann cells and axons. Also referred to as Nectin-like molecules (Necl) 1-4 and Ig Superfamily (IGSF) 4A-D, the differential expression pattern of SynCAM-1 to -4 is thought to provide adhesion signals for neuronal circuit formation. Although generally considered to influence the later stages of neural circuit formation, recent studies report that SynCAMs also affect axon guidance.
For example, in chick spinal cord the expression of IGSF4D/SynCAM-2 on floor plate cells is required for rostral turning of axons following their crossing of the midline. Additional studies showed that IGSF4A/SynCAM-1 is expressed at the cell surface of growth cones and in concert with focal adhesion kinase (FAK) regulates growth cone morphology and axodendritic contact with target neurites. Transgenic experiments also suggest that IGSF4A/SynCAM-1 specifically promotes the formation of excitatory synapses and can affect the plasticity of mature synaptic connections. Recent reports revealed that post-translational modification is an important factor governing SynCAM biology. For example, N-glycosylation of the Ig1 domain enhances IGSF4A/SynCAM-1 mediated synaptic adhesion but has the opposite effect on IGSF4D/SynCAM-2.