Abstract
During activation, T cells associate with antigen-presenting cells, a dynamic process that involves the formation of a broad area of intimate membrane contact known as the immunological synapse. The molecular intermediates that link initial antigen recognition to the cytoskeletal changes involved in this phenomenon have not yet been defined. Here we demonstrate that ezrin-radixin-moesin proteins are rapidly inactivated after antigen recognition through a Vav1-Rac1 pathway. The resulting disanchoring of the cortical actin cytoskeleton from the plasma membrane decreased cellular rigidity, leading to more efficient T cell-antigen-presenting cell conjugate formation. These findings identify an antigen-dependent molecular pathway that favors immunological synapse formation and the subsequent development of an effective immune response.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actin Cytoskeleton / ultrastructure*
-
Animals
-
Antigen Presentation
-
Antigen-Presenting Cells / immunology*
-
Blood Proteins / physiology
-
Cell Cycle Proteins*
-
Cells, Cultured
-
Cytoskeletal Proteins / physiology*
-
Humans
-
Lymphocyte Activation*
-
Membrane Proteins / physiology
-
Mice
-
Mice, Inbred BALB C
-
Mice, Knockout
-
Microfilament Proteins / physiology
-
Phosphoproteins / physiology
-
Protein Serine-Threonine Kinases / physiology
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins c-vav
-
Receptors, Antigen, T-Cell / metabolism
-
T-Lymphocytes / immunology*
-
T-Lymphocytes / ultrastructure
-
p21-Activated Kinases
-
rho GTP-Binding Proteins / metabolism
Substances
-
Blood Proteins
-
Cell Cycle Proteins
-
Cytoskeletal Proteins
-
Membrane Proteins
-
Microfilament Proteins
-
Phosphoproteins
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-vav
-
Receptors, Antigen, T-Cell
-
VAV1 protein, human
-
Vav1 protein, mouse
-
ezrin
-
moesin
-
radixin
-
PAK1 protein, human
-
Pak1 protein, mouse
-
Protein Serine-Threonine Kinases
-
p21-Activated Kinases
-
rho GTP-Binding Proteins