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.
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
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
J. Biol. Chem.
Date: Mar. 22, 2002
PubMed ID: 11784723
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