Recombinant Human Neurturin Protein

Neurturin is a member of the GDNF family of ligands, which include glial cell-derived neurotrophic factor (GDNF), Neurturin, Persephin, and Artemin. GDNF family proteins are distant members of the Transforming Growth Factor beta (TGF-beta) superfamily (1-4). Similarly to other TGF-beta family proteins, Neurturin is synthesized as a precursor protein that is cleaved at the dibasic cleavage site (RXXR) to release the carboxy-terminal domain. The carboxy-terminal domain of Neurturin contains the characteristic seven conserved cysteine residues necessary for the formation of the cysteine-knot and the single interchain disulfide bond. Biologically active human Neurturin is a disulfide-linked homodimer of the carboxy-terminal 102 amino acid residues. Mature human Neurturin shares approximately 92% amino acid sequence identity with mouse Neurturin. Mature Neurturin also shares about 40% similarities with the other three members of the GDNF family ligands (2-5). Unlike other members of TGF-beta family, bioactivities of all GDNF family ligands are mediated through a unique multicomponent receptor complex composed of high affinity ligand binding component (GFR alpha-1-GFR alpha-4) and a common signaling component (cRET receptor tyrosine kinase). Each member of the GDNF family ligands has its preferred binding protein. Neurturin preferentially binds to GFR alpha-2 but can also bind GFR alpha-1 at higher concentrations (5‑8). Neurturin had been shown to promote the survival of a variety of neurons including sympathetic, sensory, and central nervous system neurons. Neurturin is expressed in both neuronal and non-neuronal tissues. It may play a role in regulating the development and maintenance of the central and peripheral nervous systems and as well as non-neuronal systems (9).