Recombinant Mouse Netrin-G2a Fc Chimera Protein, CF

Netrin-G2a (netr: Sanskrit for "one who guides") is a 60 ‑ 75 kDa glycoprotein member of the netrin‑G/laminet subfamily, UNC-6/netrin family of axon guidance molecules (1, 2, 3). The two members of the netrin‑G subfamily (G1 and G2) are GPI‑linked and found only in vertebrates. They do not bind to either DCC or UNC5, but regulate synaptic interactions by binding to NGL-1 and NGL-2. Mouse Netrin-G2a (also called laminet-2 and NTNG2) is the shortest of three netrin‑G2 gene products (2). It is synthesized as a 530 amino acid (aa) preprocursor that contains a 17 aa signal sequence, a 490 aa mature region, and a 23 aa C‑terminal prosegment that is cleaved to give rise to a GPI‑linkage site (Gly507). The mature molecule contains one N‑terminal laminin type VI domain (aa 60 ‑ 285), plus three consecutive laminin EGF‑like regions (aa 287 ‑ 453). There are at least two splice variants, each of which show insertions after Gly352. The first (netrin‑G2b) shows a 60 aa substitution for Asn353, while the second (netrin‑G2c) shows a 35 aa substitution for Asn353. Mature mouse Netrin‑G2a shares 99% and 96% aa identity with rat and human Netrin‑G2a, respectively. Netrin‑G2a is principally expressed in neurons, including granule cells of the dentate gyrus, pyramidal cells of the hippocampus (CA1, CA3, CA4) and cells of the cerebral cortex (4, 5, 6). It appears to be a presynaptic molecule that is associated with excitatory intracortical tracts (6 ‑ 9). The ligand for Netrin‑G2a is NGL‑2/netrin‑G ligand #2, a postsynaptic 100 kDa member of the NGL family of synaptic cell adhesion molecules (8, 10). Netrin‑G2a:NGL‑2 binding is of high affinity (K_D = 2.5 nM), and appears to influence the stability of NMDA‑type glutamatergic receptors on postsynaptic membranes (4, 11). Although the exact mechanism is unclear, Netrin‑G2a ligation of NGL‑2 promotes NGL-2 interaction with PSD95 and NR1 and NR2B in the postsynaptic membrane. This leads to an association of both neuroligin‑1/2 and NMDA subunits, and the formation of functional, fixed glutamatergic receptors (5, 6, 8).