Journal
JOURNAL OF NEUROCHEMISTRY
Volume 80, Issue 6, Pages 998-1008Publisher
WILEY
DOI: 10.1046/j.0022-3042.2002.00796.x
Keywords
amphoterin; cell signalling; HMGB1; neurite outgrowth; N-glycans; RAGE
Categories
Funding
- NATIONAL CANCER INSTITUTE [P01CA071932] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS032717] Funding Source: NIH RePORTER
- NCI NIH HHS [P01-CA71932] Funding Source: Medline
- NINDS NIH HHS [R01-NS32717] Funding Source: Medline
Ask authors/readers for more resources
In this study we show that embryonic neurite growth-promoting protein amphoterin binds to carboxylated N-glycans previously identified on mammalian endothelial cells. Since amphoterin is a ligand for the receptor for advanced glycation end products (RAGE), and the ligand-binding V-domain of the receptor contains two potential N-glycosylation sites, we hypothesized that N-glycans on RAGE may mediate its interactions with amphoterin. In support of this, anti-carboxylate antibody mAbGB3.1 immunoprecipitates bovine RAGE, and PNGase F treatment reduces its molecular mass by 4.5 kDa, suggesting that the native receptor is a glycoprotein. The binding potential of amphoterin to RAGE decreases significantly in presence of soluble carboxylated glycans or when the receptor is deglycosylated. Oligosaccharide analysis shows that RAGE contains complex type anionic N-glycans with non-sialic acid carboxylate groups, but not the HNK-1 (3-sulfoglucuronyl beta1-3 galactoside) epitope. Consistent with the functional localization of RAGE and amphoterin at the leading edges of developing neurons, mAbGB3.1 stains axons and growth cones of mouse embryonic cortical neurons, and inhibits neurite outgrowth on amphoterin matrix. The carboxylated glycans themselves promote neurite outgrowth in embryonic neurons and RAGE-transfected neuroblastoma cells. This outgrowth requires full-length, signalling-competent RAGE, as cells expressing cytoplasmic domain-deleted RAGE are unresponsive. These results indicate that carboxylated N-glycans on RAGE play an important functional role in amphoterin-RAGE-mediated signalling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available