ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation.
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.
Faure
Sophie
S
Institut Cochin, Département de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale U567/Centre National de la Recherche Scientifique UMR 8104, Université René Descartes, 22 rue Méchain, 75014 Paris, France.
Salazar-Fontana
Laura Inés
LI
Semichon
Monique
M
Tybulewicz
Victor L J
VL
Bismuth
Georges
G
Trautmann
Alain
A
Germain
Ronald N
RN
Delon
Jérôme
J
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001798:Blood Proteins / Q000502:physiology; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000099149:Ezrin
D001798:Blood Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins; D000099149:Ezrin; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; C071058:moesin; C071776:radixin; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse