rhAgrin, CF (50 ug)

Background: Agrin

Agrin is a 400‑600 kDa heparan sulfate proteoglycan component of the extracellular matrix. The N-terminal half of human Agrin, which mediates ECM interactions, contains a Laminin-binding NtA domain, nine Kazal-type protease inhibitor domains, two Laminin EGF-like domains, and one SEA domain. The C‑terminal half contains four EGF-like repeats and three Laminin globular G domains. Rat Agrin lacks the NtA domain, and mouse and chick Agrin include the NtA domain only by the use of an alternate promoter. Additional isoforms are generated by alternate splicing at sites Y and Z in the C‑terminal half of rat Agrin (known as A and B, respectively in chick). Agrin isoforms that contain an insert at site Z (Z+ forms) are known as neural Agrin and are selectively produced by motoneurons. Other isoforms are known as muscle Agrin and are additionally expressed in non-neuronal tissues, particularly in basement membranes of the lung and kidney (1-3). This recombinant protein consists of the C‑terminal half of human Agrin corresponding to the Z- isoform of rat Agrin. It shares 60%, 78%, and 80% amino acid sequence identity with comparable regions of chick, mouse, and rat Agrin, respectively. The C‑terminal half of Z- and Z+ Agrin binds to alpha ‑Dystroglycan and mediates adhesion between motoneurons and myotubes at the neuromuscular junction (NMJ) (4-6). In contrast, only Z+ Agrin is effective at inducing clustering of the postsynaptic Acetylcholine Receptor (AChR) and presynaptic motoneuron differentiation (7, 8). Agrin-induced AChR clustering requires a myotube receptor complex that contains alpha ‑Dystroglycan, MuSK, and LRP4 (4, 9-11). Agrin exhibits many functions in addition to NMJ development. It is enriched in senile Alzheimer's disease plaques where it binds the A beta (1‑40) peptide and promotes amyloid fibril formation (12). It regulates neuronal excitability by binding and inhibiting the alpha 3 subunit of the neuronal Na/K ATPase (13). It functions as an epithelial cell attachment receptor for HIV-1 through interactions with the gp41 coat protein (14). During T cell activation, Agrin contributes to formation of the immunological synapse and regulates the threshold of T cell activation (15).