The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs).
The human receptor for advanced glycation endproducts (RAGE) is a multiligand cell surface protein belonging to the immunoglobulin superfamily, and is involved in inflammatory and immune responses. Most importantly, RAGE is considered a receptor for HMGB1 and several S100 proteins, which are Damage-Associated Molecular Pattern molecules (DAMPs) released during tissue damage. In this study we show that the Ager gene coding for RAGE first appeared in mammals, and is closely related to other genes coding for cell adhesion molecules (CAMs) such as ALCAM, BCAM and MCAM that appeared earlier during metazoan evolution. RAGE is expressed at very low levels in most cells, but when expressed at high levels, it mediates cell adhesion to extracellular matrix components and to other cells through homophilic interactions. Our results suggest that RAGE evolved from a family of CAMs, and might still act as an adhesion molecule, in particular in the lung where it is highly expressed or under pathological conditions characterized by an increase of its protein levels.
Chromatin Dynamics Unit, San Raffaele University and Research Institute, Milano, Italy.
Luca
L
Sessa
Chromatin Dynamics Unit, San Raffaele University and Research Institute, Milano, Italy.
Elena
E
Gatti
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, Milano, Italy.
Filippo
F
Zeni
Chromatin Dynamics Unit, San Raffaele University and Research Institute, Milano, Italy.
Antonella
A
Antonelli
Chromatin Dynamics Unit, San Raffaele University and Research Institute, Milano, Italy.
Alessandro
A
Catucci
Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
Michael
M
Koch
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, Milano, Italy.
Giulio
G
Pompilio
Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
Günter
G
Fritz
Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, Milano, Italy.
Angela
A
Raucci
Chromatin Dynamics Unit, San Raffaele University and Research Institute, Milano, Italy.
Marco E
ME
Bianchi
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics*; D019295:Computational Biology; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005455:Fluorescent Antibody Technique; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D020349:Surface Plasmon Resonance
D015815:Cell Adhesion Molecules; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic