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Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; During activation, T lymphocytes become
motile cells, switching from a spherical to a polarized
shape. Chemokines and other chemotactic cytokines induce lymphocyte polarization with the formation of a
uropod in the rear pole, where the adhesion receptors intercellular adhesion molecule-1 (ICAM-1), ICAM-3,
and CD44 redistribute. We have investigated membrane-cytoskeleton interactions that play a key role in
the redistribution of adhesion receptors to the uropod.
Immunofluorescence analysis showed that the ERM
proteins radixin and moesin localized to the uropod of
human T lymphoblasts treated with the chemokine
RANTES (regulated on activation, normal T cell expressed, and secreted), a polarization-inducing agent; radixin colocalized with arrays of myosin II at the neck
of the uropods, whereas moesin decorated the most distal part of the uropod and colocalized with ICAM-1,
ICAM-3, and CD44 molecules. Two other cytoskeletal
proteins, Department of
Pathology, Stanford University, Stanford, California 94305-5324; § Tumor Immunology Program, German Cancer Research
Center, Heidelberg, Germany D-69120; and Servei Inmunología, Hospital Clinic, 08036 Barcelona, Spain
-actin and 
-tubulin, clustered at the cell
leading edge and uropod, respectively, of polarized lymphocytes. Biochemical analysis showed that moesin
coimmunoprecipitates with ICAM-3 in T lymphoblasts
stimulated with either RANTES or the polarization-
inducing anti-ICAM-3 HP2/19 mAb, as well as in the
constitutively polarized T cell line HSB-2. In addition, moesin is associated with CD44, but not with ICAM-1,
in polarized T lymphocytes. A correlation between the
degree of moesin-ICAM-3 interaction and cell polarization was found as determined by immunofluorescence and immunoprecipitation analysis done in parallel. The moesin-ICAM-3 interaction was specifically
mediated by the cytoplasmic domain of ICAM-3 as revealed by precipitation of moesin with a GST fusion protein containing the ICAM-3 cytoplasmic tail from
metabolically labeled Jurkat T cell lysates. The interaction of moesin with ICAM-3 was greatly diminished
when RANTES-stimulated T lymphoblasts were pretreated with the myosin-disrupting drug butanedione
monoxime, which prevents lymphocyte polarization.
Altogether, these data indicate that moesin interacts
with ICAM-3 and CD44 adhesion molecules in uropods
of polarized T cells; these data also suggest that these
interactions participate in the formation of links between membrane receptors and the cytoskeleton,
thereby regulating morphological changes during cell
locomotion.
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