SynCAMs - From axon guidance to neurodevelopmental disorders

•SynCAMs, initially identified as synaptic CAMs, also affect axon guidance.•SynCAMs have been linked to neurodevelopmental disorders.•All steps in neural circuit formation contribute to neurodevelopmental disorders.

Many cell adhesion molecules are located at synapses but only few of them can be considered synaptic cell adhesion molecules in the strict sense. Besides the Neurexins and Neuroligins, the LRRTMs (leucine rich repeat transmembrane proteins) and the SynCAMs/CADMs can induce synapse formation when expressed in non-neuronal cells and therefore are true synaptic cell adhesion molecules. SynCAMs (synaptic cell adhesion molecules) are a subfamily of the immunoglobulin superfamily of cell adhesion molecules. As suggested by their name, they were first identified as cell adhesion molecules at the synapse which were sufficient to trigger synapse formation. They also contribute to myelination by mediating axon-glia cell contacts. More recently, their role in earlier stages of neural circuit formation was demonstrated, as they also guide axons both in the peripheral and in the central nervous system. Mutations in SynCAM genes were found in patients diagnosed with autism spectrum disorders. The diverse functions of SynCAMs during development suggest that neurodevelopmental disorders are not only due to defects in synaptic plasticity. Rather, early steps of neural circuit formation are likely to contribute.

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