GDNF Family

1. GDNF Family Overview GDNF, neurturin, persephin and artemin are a class of secretory proteins with similar structure and function. They all have 7 conserved cysteine residues, with similar spatial structure, nucleotide sequence and amino acid sequence with high homology. They constitute a subfamily of the transforming growth factor beta (TGF-beta) superfamily, which are similar in physiological functions, receptors, signal transduction pathways, and so on. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1. Persephin promotes the survival and growth of central dopaminergic and motor neurons, and is also involved in kidney development. Artemin promotes the survival and growth of various peripheral and central neurons, including sympathetic and dopaminergic neurons. Neurturin exerts a positive effect on the survival of a variety of neurons and possibly other cell types. Members of GDNF family Table 1. GDNF family related products ARTN GDNF NRTN GDNF Ligands PSPN GFRA1 GFRA2 GFRA3 GDNF Receptor GFRA4 GFRAL GDNF  The glial cell derived neurotrophic factor (GDNF) is a neurotrophic factor isolated and purified from the conditioned medium of rat glial cell line B49 by

2. Lin et al. (1993), and is named after that. The GDNF gene of rat and human was cloned by using the amino terminal sequence of purified GDNF as a probe. The human GDNF precursor protein is 211 amino acid residues (including 19 amino acids of signal peptide). After processing, it forms a secretory mature protein and has 134 amino acids. It is a glycosylated disulfide-linked homodimeric protein, and its molecular weight is 32~34kD, which is an alkaline protein. NRTN  Neurturin (NRTN) is a protein. Neurturin belongs to the glial cell-line derived neurotrophic factor (GDNF) family of neurotrophic factors, which regulate the survival and function of neurons. Neurturin acts as a growth factor places it in the TGF-beta (transforming growth factor) subfamily along with its homologs persephin, artemin, and GDNF. It is also considered as a trophic factor and is critical in the development and growth of neurons in the brain. Neurotrophic factors like neurotrophic factors have been tested in several clinical trials setting for the potential treatment of neurodegenerative diseases, specifically Parkinson’s disease. PSPN  The amino acid sequence of persephin (PSPN) has about 40% homology with NRTN and GDNF. It has not only seven conserved cysteines in the TGF-beta family, but also a conservative sequence only between NRTN and GDNF. It was found that the expression of PSPN in embryonic and adult rat tissues was extremely low, and the content of mRNA in each tissue was relatively high, which suggested that the regulation of mRNA shear processing may play an important role in regulating the expression of PSPN protein. The study of the PSPN function has just begun. Figure 1. Tertiary structure of human artemin. https://www.creative-diagnostics.com/gdnf-family.htm