Glial Cell Line-derived Neurotrophic Factor (GDNF) is a recently discovered neurotrophic factor that has been shown to promote the survival of various neuronal subpopulations in both the central as well as the peripheral nervous systems at different stages of their development. Neuronal subpopulations that have been shown to be affected by GDNF include motoneurons, midbrain dopaminergic neurons, Purkinje cells and sympathetic neurons.
Native GDNF, a disulfide-linked homodimeric glycoprotein, is a novel member of the TGF-β superfamily. Rat GDNF cDNA encodes a 211 amino acid residue prepropeptide that is processed to yield a dimeric protein composed of two 134 amino acid residue subunits. The GDNF sequence contains two potential glycosylation sites and insect cell-expressed recombinant rat GDNF proteins are glycosylated. Mature rat and human GDNF exhibit approximately 93% amino acid sequence identity and show considerable species cross-reactivity. Cells known to express GDNF include Sertoli cells, type 1 astrocytes, Schwann cells, neurons, pinealocytes and skeletal muscle cells.
A DNA sequence encoding the rat GDNF protein sequence (Lin, L-F. et al 1993, Science 260:1130 - 1132) was inserted in a baculovirus expression vector and expressed in Sf 21 insect cells.