Netrin-1, Recombinant, Human, Fc Chimera (NTN1, NTN1L, Netrin 1)

Human Netrin-1 (netr: Sanskrit for пїЅone who guidesпїЅ) is a 75kD glycoprotein that is closely related to the laminin y domain and functions as a chemoattractive or chemorepulsive guidance cue in the central nervous system (CNS) during development (1-2). The protein is synthesized as a 604aa precursor that contains a 24aa signal sequence and a 580aa mature chain. Residues 46-283 constitute a laminin N-terminal domain (domain VI), while\n285-453 make up three laminin-type epidermal growth factor-like domains. There is a final domain that runs from aa487-601 that qualifies as a Netrin- 1 like domain. It is also known as domain C in the context of C. elegans. There are four potential sites for N-linked glycosylation. Human Netrin-1 is 99% aa identical to mouse and rat Netrin-1. Netrin-1 is expressed in adult and embryonic tissues. In the adult, the protein is expressed in Schwann cells, oligodendrocytes and multiple neurons. In embryonic tissues, Netrin-1 is found in somatic mesoderm, heart, branchial pouch, and neuroepithelium. Netrin-1 is a secreted protein that, in addition to its involvement in outgrowth and migration orientation in the developing CNS, plays a significant role in the morphogenesis of endothelial cells and vascular smooth-muscle cells. It is also involved in the processes of cytoskeleton reorganization, angiogenesis, epithelial cell adhesion, and cell migration in the lungs, mammary gland, and pancreas (1, 3). Netrin-1 effects are controlled through different transmembrane receptors (2). Four of the receptors exist in the Unc-5 (Unc=uncontrolled behaviorally) family of proteins, and these include Unc5h1, Unc5h2, Unc5h3/RCM, and Unc5h4. There are also two receptors that belong to the UNC-40 family of molecules. The first is DCC (deleted in colorectal cancer), and the second is neogenin (newly-generated). UNC-5 receptors are noted to mediate the attraction response of axons and netrins. However, UNC-5 molecules, when co-expressed with DCC in the presence of Netrin-1, will mediate repulsion by varying cellular calcium levels (3). The adenosine A2b receptor may also be involved in chemoattraction, either by binding directly with Netrin-1 or by serving as a co-receptor for DCC. These receptors are known as dependence receptors because they depend on their ligand, in this case Netrin-1, for survival (4). Unbound, the receptors induce a specific death signal (4). It is the dysregulation of these receptor systems that may have important roles in tumor biology. DCC and UNC5 proteins make up a system for either initiating or inhibiting apoptosis (4), and it is now believed that Netrin-1 and its dependence receptors play a major role in tumor biology (4-6).\n\nSource:\nRecombinant corresponding to aa22-604 (HPGGGSGGGSGGGS) of human Netrin-1, fused with 6-His tag at N-terminal, expressed in mouse myeloma cell line, NS0.\n\nMolecular Weight: \n~67.5kD\n\nEndotoxin Level:\n(same/less than)1EU/1ug (LAL)\n\nBiological Activity:\nMeasured by its binding ability in a functional ELISA. When recombinant rat UNC5H2 Fc Chimera is immobilized at 5ug/ml, recombinant human Netrin-1 binds with an apparent KD < 1nM.\nMeasured in a cell proliferation assay using RT4-D6P2T rat Schwann cells (ATCC: CRL-2768). The ED50 for this effect is typically 0.5-2ug/ml.\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with PBS. Aliquot to avoid repeated freezing and thawing. 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.

Prices direct from United States Biological

Quick response times

Exclusive Biosave savings/discounts

SPECIFICATIONS

Catalog Number

N1193-16F

Size

25ug

Form

Supplied as a lyophilized powder in PBS, EDTA. Reconstitute with PBS to 100ug/ml.

Purity

~95% (SDS-PAGE)

References

1. Dakouane-Giudicelli, M. et al. (2010) J. Histochem. Cytochem. 58:73. 2. Masuda, T. et al. (2008) J. of Neurosci. 28:10380. 3. Bernet, A. and P. Mehlen (2007) Bull. Cancer 94:E12. 4. Cirulli, V. and M. Yebra, (2007) Nat. Rev. Mol. Cell. Biol. 8:296. 5. Dumartin, L. et al. (2010) Gastroenterology 137:1595. 6. Mazelin, L. et al. (2004) Nature 431:80.