Agrin: an extracellular matrix heparan sulfate proteoglycan involved in cell interactions and synaptogenesis

Recent studies have documented important roles for heparan sulfate proteoglycans in the control of nervous system development. Agrin is an extracellular matrix protein identified and named based on its involvement in the aggregation of acetylcholine receptors (AChRs) during synaptogenesis at the neuromuscular junction. Recent studies have demonstrated that agrin is a large extracellular heparan sulfate proteoglycan, with a molecular mass in excess of 500 kDa and a protein core of 220 kDa. Emerging evidence indicates that agrin's function is not limited to its role in AChR aggregation during synaptogenesis, as the majority of agrin expression occurs in the developing central nervous system, especially in developing axonal tracts. This review examines recent studies suggesting a role for agrin in the regulation of cell-cell interactions, most notably by its ability to interact with the neural cell adhesion molecule. In addition, other potential roles for the heparan sulfate chains of agrin during nervous system development are explored.