The Receptor for Advanced Glycation End Products (RAGE) Is a Cellular Binding Site for Amphoterin
MEDIATION OF NEURITE OUTGROWTH AND CO-EXPRESSION OF RAGE AND AMPHOTERIN IN THE DEVELOPING NERVOUS SYSTEM (*)
- Osamu Hori,
- Jerold Brett,
- Timothy Slattery(1),
- Rong Cao,
- Jinghua Zhang,
- Jing Xian Chen,
- Mariko Nagashima(1),
- Erik R. Lundh(1),
- Sharmila Vijay(1),
- Di Nitecki(1),
- John Morser(1),
- David Stern and
- Ann Marie Schmidt(§)
- From the Departments of Physiology, Surgery, and Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032 and
- (1) Berlex Biosciences, Richmond, California 94804
- § To whom correspondence should be addressed: P& 11-518, Columbia University, College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032. Tel.: 212-305-1615; Fax: 212-305-5337.
Abstract
The receptor for advanced glycation end products (RAGE), a newly-identified member of the immunoglobulin superfamily, mediates
interactions of advanced glycation end product (AGE)-modified proteins with endothelium and other cell types. Survey of normal
tissues demonstrated RAGE expression in situations in which accumulation of AGEs would be unexpected, leading to the hypothesis
that under physiologic circumstances, RAGE might mediate interaction with ligands distinct from AGEs. Sequential chromatography
of bovine lung extract identified polypeptides with Mr values of ≈12,000 (p12) and ≈23,000 (p23) which bound RAGE. NH
-terminal and internal protein sequence data for p23 matched that reported previously for amphoterin. Amphoterin purified
from rat brain or recombinant rat amphoterin bound to purified sRAGE in a saturable and dose-dependent manner, blocked by
anti-RAGE IgG or a soluble form of RAGE (sRAGE). Cultured embryonic rat neurons, which express RAGE, displayed dose-dependent
binding of 
I-amphoterin which was prevented by blockade of RAGE using antibody to the receptor or excess soluble receptor (sRAGE). A
functional correlate of RAGE-amphoterin interaction was inhibition by anti-RAGE F(ab′)
and sRAGE of neurite formation by cortical neurons specifically on amphoterin-coated substrates. Consistent with a potential
role for RAGE-amphoterin interaction in development, amphoterin and RAGE mRNA/antigen were co-localized in developing rat
brain. These data indicate that RAGE has physiologically relevant ligands distinct from AGEs which are likely, via their interaction
with the receptor, to participate in physiologic processes outside of the context of diabetes and accumulation of AGEs.
Footnotes
-
↵* This work was supported by United States Public Health Service Grants AG00602 and HL21006, the Council for Tobacco Research, the American Heart Association, New York affiliate, and the Juvenile Diabetes Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- RAGE
-
receptor for advanced glycation end product
- AGE
-
advanced glycation end product
- sRAGE
-
soluble RAGE
- HPLC
-
high performance liquid chromatography
- PAGE
-
polyacrylamide gel electrophoresis.
-
↵2J. L. Wautier, C. Zoukourian, O. Chappey, M. P. Wautier, P. J. Guillausseau, R. Cao, O. Hori, D. Stern, and A. M. Schmidt, manuscript submitted for publication.
-
↵3A. M. Schmidt, O. Hori, and D. Stern, unpublished observation.
-
- Received June 30, 1995.
- Revision received August 22, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
