Localization of the ezrin binding epitope for glycated proteins.
ERM proteins (ezrin, radixin, and moesin) have recently been identified as a new class of AGE-binding proteins. ERM proteins link the plasma membrane with the actin cytoskeleton and regulate cell shape, motility, adhesion, and signal transduction. ERM proteins have three structural domains: the N-terminal domain, a coiled midregion, and the C-terminal domain. The N-terminal domain binds to a number of plasma membrane ligands and is involved in signal transduction, while the C-domain binds to actin filaments. Binding studies with isolated structural domains showed that glycated proteins bind to an epitope within the N-terminal domain of ezrin (aa 1-324). It is postulated that some of the cellular effects of AGEs leading to diabetic complications may be mediated by binding to this region of ezrin, thereby interrupting the cross-linking between the plasma membrane and actin cytoskeleton and downstream signaling pathways. Indeed, changes in actin arrangement, cell shape, and adhesion have been described in diabetes, and AGE-BSA inhibits ezrin-dependent tubulogenesis of LLC-PK1 proximal tubular cells. For future development of antagonists, further identification of the ezrin-binding epitope for glycated proteins is required.
McRobert
E Anne
EA
Present address and address for correspondence: E. Anne McRobert, Central and Eastern Clinical School, Department of Medicine, Monash University, AMREP, Alfred Hospital, Prahran, Vic 3181, Australia. mcrobert@unimelb.edu.au.
Tikoo
Anjali
A
Gallicchio
Marisa A
MA
Cooper
Mark E
ME
Bach
Leon A
LA
D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D048909:Diabetes Complications / Q000378:metabolism; D000939:Epitopes / Q000032:analysis; D004912:Erythrocytes / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D000099149:Ezrin
D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D000939:Epitopes; D017127:Glycation End Products, Advanced; D010750:Phosphoproteins; D011506:Proteins; D000099149:Ezrin