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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

Authors

  • Serrador JM
  • Vicente-Manzanares M
  • Calvo J
  • Barreiro O
  • Montoya MC
  • Schwartz-Albiez R
  • Furthmayr H
  • Lozano F
  • S├ínchez-Madrid F

Journal

The Journal of biological chemistry

Publication Data

March 22, 2002

Associated Grants

None

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