Immunoglobulin cell adhesion molecules of the Ig-FNIII type and neurodevelopment

Abstract The nervous system functions by virtue of precisely positioned neurons with fine-tuned circuitry. The formation of these structures depends largely on interactions and communication between different cells mediated by proteins on the extracellular membrane. Proteins carrying the immunoglobulin amino acid motif are manifold and encountered in all species, organ systems and cell-types, where they are engaged in many biological processes. About eight brain-expressed subclasses combine the Ig motif with fibronectin type-3 (FNIII) domains and form the FN-type IgCAMs, in total consisting of over a hundred distinct protein (iso)forms. In the developing nervous system, they serve as cell adhesion molecules, (co)receptors, ligands, tyrosine kinases and phosphatases. These activities are recognized in the involvement of FN-type IgCAMs in neurodevelopmental processes as neurite outgrowth, axon elongation and steering, neuronal and glial migration, neuron–glia interaction, synaptogenesis and synaptic plasticity. In accord with these elementary neurodevelopmental functions, mutations in genes encoding these FN-type IgCAMs have been encountered in several neurodevelopmental disorders and syndromes, including mental retardation and autism.