Contactin-2/TAG-1, active on the front line for three decades

Contactin-2/transiently expressed axonal surface glycoprotein-1 (TAG-1) is a cell adhesion molecule belonging to the immunoglobulin superfamily (IgSF). It has six immunoglobulin-like extracellular domains and four fibronectin III-like ones, with anchoring to the cell membrane through glycosylphosphatidyl inositol. Contactin-2/TAG-1 is expressed in specific neurons transiently on the axonal surface during the fetal period. In postnatal stages, Contactin-2/TAG-1 is expressed in cerebellar granule cells, hippocampal pyramidal cells, and the juxtaparanodal regions of myelinated nerve fibers. In the embryonic nervous system, Contactin-2/TAG-1 plays important roles in axonal elongation, axonal guidance, and cellular migration. In the postnatal nervous system, it also plays an essential role in the formation of myelinated nerve fibers. Moreover, Contactin-2/TAG-1 has been linked to autoimmune diseases of the human nervous system. Taken together, Contactin-2/TAG-1 plays a central role in a variety of functions from development to disease.