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Localization of the Ezrin Binding Epitope for Glycated Proteins
Author(s) -
McROBERT E ANNE,
TIKOO ANJALI,
GALLICCHIO MARISA A.,
COOPER MARK E.,
BACH LEON A.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1333.070
Subject(s) - ezrin , moesin , radixin , microbiology and biotechnology , ferm domain , cytoskeleton , actin cytoskeleton , chemistry , actin , signal transduction , epitope , cell adhesion , phosphotyrosine binding domain , plasma protein binding , actin binding protein , membrane protein , biology , biochemistry , cell , membrane , integral membrane protein , antigen , immunology , sh2 domain , receptor tyrosine kinase
A bstract : 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.