ApoE R2, Recombinant Human

Cleavage of ApoE R2 by g-secretase, metalloproteases, and furin-like enzymes results in the liberation of the cytoplasmic, extracellular, and ligand binding domains. The cytoplasmic NPxY motif binds to PTB domain-containing adaptor proteins. Among these, FE65 and PSD95 couple ApoE R2 with APP or the NMDA receptor, respectively. ApoE R2 and NMDA receptor ligands modulate adaptor interactions, NMDA-mediated ion currents, and the proteolytic processing of both ApoE R2 and APP. ApoE R2 and the NMDA receptor also associate extracellularly. ApoE R2 binds ApoE-containing lipoproteins and the large modular protein, reelin. Reelin signaling through ApoE R2 is critical for neuronal migration and positioning in the developing brain. In the adult brain, ApoE R2 functions in hippocampal synapse maturation, synaptic plasticity, and memory formation.ApoE R2 is also expressed at the neuromuscular junction but does not appear to participate in the development or function of that structure. Deficits in ApoE R2, reelin, and ApoE function have been linked to several cognitive and mood disorders. \n\nHuman ApoE R2 has a 794 aa extracellular domain (ECD) and a 116 aa cytoplasmic region. The ECD contains seven LDLR class A repeats followed by two EGF-like repeats, five LDLR class B repeats, and a region rich in O-linked glycosylation. Alternatively spliced variants of human \nApoE R2 have deletions of LDLR-A repeats # 4-7, the O-linked glycosylation region, or approximately half of the cytoplasmic domain. \n\nA DNA sequence encoding the signal peptide from human CD33 joined with the extracellular domain of human ApoE R2 sequence (Ala 32-Lys 818) was fused with a 10X histidine tag at the carboxyl-terminus. The chimeric protein was expressed in a Chinese hamster ovary cell line. \n\nEndotoxin Level: (same/less than) 1 EU/ug of protein as determined by the LAL method. \n\nBiological Activity: \nMeasured by its ability to compete with biotinylated rhApoE R2 for binding to rmReelin in a functional ELISA type binding assay. \n\nStorage and Stability:\nAliquot to avoid repeated freezing and thawing and freeze at -70 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Aliquots are stable for at least 12 months.

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SPECIFICATIONS

Catalog Number

A2299-76T

Size

50ug

Applications

ELISA

Form

Supplied as a lyophilized powder from PBS. Reconstitute with PBS to a concentration of 0.1mg/ml.

Purity

> 90%, as determined by SDS-PAGE and visualized by silver stain. Endotoxin: < 1.0 EU per 1ug of protein as determined by the LAL method.

References

1. Qiu, S. et al., 2006, Neurobiol. Learn. Mem. 85:16. 9. Hoe, H.S. et al., 2006, J. Biol. Chem. 281:24521. \n2. May, P. et al., 2005, Cell. Mol. Life Sci. 62:2325. 10. Hoe, H.-S. et al., 2006, J. Biol. Chem. 281:3425. \n3. Kim, D.H. et al., 1997, J. Biol. Chem. 272:8498. 11. Beffert, U. et al., 2005, Neuron 47:567. \n4. May, P. et al., 2003, J. Biol. Chem. 278:37386. 12. Hoe, H.-S. et al., 2005, Mol. Cell. Biol. 25:9259. \n5. Koch, S. et al., 2002, EMBO J. 21:5996. 13. D

Additional Info

Recognizes human ApoE R2. Species sequence homology: mouse and rat 89%. Crossreactivity: 46% human LDL R and 48% VLDL R.