Agrin (AGRN) is a >400 kDa multi-domain heparan sulfate proteoglycan found in basement membranes. It is a critical organizer of postsynaptic differentiation at the skeletal neuromuscular junction; synaptogenesis is profoundly disrupted in its absence (Gautam et al. 1996). Two alternate N-termini exist. The predominant longer LN form (Burgess et al. 2000) starts with a secretion signal sequence and a laminin-binding domain (Denzer et al. 1995, Kammerer et al. 1999); the shorter SN form associates with the plasma membrane (Burgess et al. 2000, Neumann et al. 2001). Following the SN or LN regions are 8 follistatin repeats, known to bind growth factors and inhibit proteases in other proteins. The central region has two repeats homologous to domain III of laminin. The C-terminal portion, which is responsible for the molecule's known signaling functions, contains four EGF repeats and three LG (G) domains homologous to those found in laminin alpha chains, neurexins and slits (Timpl et al. 2000).
The LG domains bind alphaVbeta1 and another beta1-containing integrin (Martin & Sanes 1997, Burgess et al. 2002, Bezakova & Ruegg 2003). The N-terminus of the LN form of AGRN binds to the laminin gamma-1 subunit (Denzer et al. 1997, Kammerer et al. 1999). This may indirectly bind AGRN to integrins on the cell surface (Bezakova & Ruegg 2003).