Rho regulates T cell receptor ITAM-induced lymphocyte spreading in an integrin-independent manner.
T cell receptor (TCR) engagement increases integrin-mediated adhesion to APC, resulting in the stabilization of the T cell : APC interaction and the close apposition of the two cell membranes. Here we show that engagement of either the TCR or CD3 chimeras with immobilized antibodies causes the rapid spreading of T cells in an integrin-independent fashion. This effect concurs with the polymerization of the actin cytoskeleton and is dependent on the integrity of the immunoreceptor tyrosine-based activation motifs of the CD3 subunits. Expression of a dominant negative mutant of RhoA, as well as the Rho-specific inhibitor C3 toxin, abolished TCR-induced spreading. In contrast, constitutively active or dominant negative forms of Rac and Cdc42 did not affect cell spreading. We conclude that signals emanating from the TCR can directly induce T cell spreading, independently of integrins, and via a Rho-dependent reorganization of the actin cytoskeleton.
Borroto
A
A
Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Madrid, Spain.
Gil
D
D
Delgado
P
P
Vicente-Manzanares
M
M
Alcover
A
A
Sánchez-Madrid
F
F
Alarcón
B
B
D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D017252:CD3 Complex / Q000737:chemistry* / Q000502:physiology; D016827:CD8 Antigens / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D000199:Actins; D017252:CD3 Complex; D016827:CD8 Antigens; D016023:Integrins; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein