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A novel serine-rich motif in the intercellular adhesion molecule 3 is critical for its ezrin/radixin/moesin-directed subcellular targeting.

Intercellular adhesion molecule 3 (ICAM-3) is a leukocyte-specific receptor involved in primary immune responses. We have investigated the interaction between ICAM-3 and ezrin/radixin/moesin (ERM) proteins and its role in LFA-1-induced cell-cell interactions and membrane positioning of ICAM-3 in polarized migrating lymphocytes. Protein-protein binding assays demonstrated a phosphatidylinositol 4,5-bisphosphate-induced association between ICAM-3 and the amino-terminal domain of ERM proteins. This interaction was not essential for the binding of ICAM-3 to LFA-1. Dynamic fluorescence videomicroscopy studies of cells demonstrated that moesin and ICAM-3 coordinately redistribute on the plasma membrane during lymphocyte migration. Furthermore, overexpression of the amino-terminal domain of moesin, which lacks the consensus moesin actin-binding site, caused the subcellular mislocalization of ICAM-3. A CD4 chimerical protein containing the cytoplasmic tail of ICAM-3 was targeted to the trailing edge. Point mutation of Ser(487), Ser(489), and Ser(496) to alanine in the juxtamembrane region of ICAM-3 significantly impaired both ERM binding and polarization of ICAM-3. ERM-directed polarization of ICAM-3 was also impaired by phosphorylation-like mutation of Ser(487) and Ser(489), but not of Ser(496). Our results underscore the key role of specific serine residues within the cytoplasmic region of ICAM-3 for its ERM-directed positioning at the trailing edge of motile lymphocytes.

Pubmed ID: 11784723 RIS Download

Mesh terms: Alanine | Amino Acid Motifs | Amino Acid Sequence | Animals | Antigens, CD | Antigens, CD4 | Antigens, Differentiation | Blood Proteins | Blotting, Western | Cell Adhesion Molecules | Cell Communication | Cell Line | Cell Membrane | Cell Movement | Cytoplasm | Cytoskeletal Proteins | Electrophoresis, Polyacrylamide Gel | Glutathione Transferase | Green Fluorescent Proteins | Humans | K562 Cells | Luminescent Proteins | Lymphocytes | Membrane Proteins | Mice | Microfilament Proteins | Microscopy, Fluorescence | Microscopy, Video | Molecular Sequence Data | Phosphoproteins | Phosphorylation | Plasmids | Precipitin Tests | Protein Binding | Protein Biosynthesis | Protein Structure, Tertiary | Recombinant Fusion Proteins | Sequence Homology, Amino Acid | Serine | Transfection

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