Glial Derived Neurotrophic Factor (GDNF) Recombinant, Human

GDNF is a disulfide-linked homodimeric neurotrophic factor structurally related to Artemin, Neurturin and Persephin. These proteins belong to the cysteine-knot superfamily of growth factors that assume stable dimeric protein structures. GDNF signals through a multicomponent receptor system, composed of a RET and one of the four GFRalpha (alpha1-alpha4) receptors. GDNF specifically promotes dopamine uptake and survival and morphological differentiation of midbrain neurons. Using Parkinson's disease mouse model, GDNF has been shown to improve conditions such as bradykinesia, rigidity, and postural instability. The functional human GDNF ligand is a disulfide-linked homodimer, of two 15kD polypeptide chains called monomers. Each monomer contains seven conserved cysteine residues, one of which (Cys101) is used for inter-chain disulfide bridging and the others are involved in intramolecular ring formation known as the cysteine knot configuration.\n\nBiological Activity:\nAssay#1: \nThe ED50 as determined by the dose-dependent dopamine uptake by rat ventral mesencephalic cultures was found to be in the range of 5-10ng/ml.\nAssay #2: \nThe ED50 was determioned by the proliferation of rat C6 cells is (same/less than)0.1ng/ml, cooresponding to a specific activity of (same/more than)1x10e7 units/mg.\n\nAA Sequence: MSPDKQMAVL PRRERNRQAA AANPENSRGK GRRGQRGKNR GCVLTAIHLN VTDLGLGYET KEELIFRYCS GSCDAAETTY DKILKNLSRN RRLVSDKVGQ ACCRPIAFDD DLSFLDDNLV YHILRKHSAK RCGCI\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with sterile ddH2O with a carrier protein. Aliquot and store at -20 degrees C. Reconstituted product is stable for 6 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

G2036

Size

2ug

Form

Supplied as a lyophilized powder from 10mM sodium citrate, 150mM sodium chloride. Reconstitute in sterile dH2O with a carrier protein to a concentration of 0.1-1mg/ml

Purity

(same/more than) 98% by SDS-PAGE and HPLC analyses. Endotoxin: (same/less than) 0.1ng/ug (1EU/ug)

References

1. Bedirian A: Pleckstrin homology and phosphotyrosine-binding domain-dependent membrane association and tyrosine phosphorylation of Dok-4, an inhibitory adapter molecule expressed in epithelial cells. Journal of Biological Chemistry; 279(18):19335-49 (4/30/2004). 2. Mikhail Paveliev: GDNF family ligands activate multiple events during axonal growth in mature sensory neurons. Mol. Cell. Neuroscience. Vol: 25 (3) pp. 453-459 (3/1/2004). 3. Yu LY: GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway. Journal of Cell Biology; 163(5):987-97 (12/8/2003). 4. Amanda Barlow: Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron, Vol: 40 pp. 905-916 (12/4/2003). 5. Svend Kjaer: Identification of a surface for binding to the GDNF-GFR alpha 1 complex in the first cadherin-like domain of RET. J. Bio. Chem. Vol: 278 (48) pp. 47898-47904 (11/28/2003). 6. Chang-Yu Wang: Regulation of neuromuscular synapse development by glial cell line-derived neurotrophic factor and neurturin. J. Bio. Chem. Vol: 277 (12) pp. 10614-10625 (3/22/2002). 7. Chuan-ju Liu: Direct interaction with contactin targets voltage-gated sodium channel Na(v)1.9/NaN to the cell membrane. J. Bio. Chem. Vol: 276 (49) pp. 46553-46561 (12/7/2001). 8. Gu Y: Biochemical and Biological Characterization of a Human RAC2 GTPase Mutant Associated with Phagocytic Immunodeficiency. J. Biol Chem: Vol 276 (19) pp.15929-15938 (5/11/2001). 9. Trupp M: Ret-dependent and -independent Mechanisms of Glial Cell Line-derived Neurotrophic factor Signaling in Neuronal Cells. J.Biol Chem, Volume 274, Issue 30, pp.20885-20894 (7/23/1999). 10. Rossi J: Retarded Growth and Deficits in the Enteric and Parasympathetic Nervous System in Mice Lacking GFRa2, a Functional Neurturin Receptor. Neuron, Volume 22. Pp.243-252 (2/1/1999). 11. Martin G. Hanson: Cyclic AMP Elevation Is Sufficient to Promote the Survival of Spinal Motor Neurons In Vitro. The J. of Neuroscience Vol: 18(18): pp.7361-7371 (9/15/1998). 12. Struder L: Transplantation of Expanded Mesencephalic precursors leads to recovery in parkinsonian rats. Nature. Neuroscience. Volume 1. Number 4 (8/1/1998). 13. Liou JC: Regulation of quantal secretion by neurotrophic factors at developing motoneurons in Xenopus cell cultures. Journal of Physiology. 503.1.pp.129-139 (1/1/1997).