ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation

Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, Germain RN and Delon J
Source: Nat Immunol
Publication Date: (2004)
Issue: 5(3): 272-279
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, human peripheral blood unstim.
Species: human
Tissue Origin: blood
Primary human peripheral blood T cells (PBTs) were nucleofected with expression vectors for GFP-tagged RhoA, Rac1, and Cdc42, as well as with expression vectors for mutated or dominant negative forms of these proteins.
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.