Role of Fyn in the rearrangement of tubulin cytoskeleton induced through TCR.
The translocation of the microtubule-organizing center (MTOC), its associated signaling complex, and the secretory apparatus is the most characteristic early event that involves the tubulin cytoskeleton of T or NK cells after their interaction with APC or target cells. Our results show that Fyn kinase activity is essential for MTOC reorientation in an Ag-dependent system. Moreover, T cells from Fyn-deficient mice are unable to rearrange their tubulin cytoskeleton in response to anti-CD3-coated beads. Analysis of conjugates of T cells from transgenic OT-I mice with dendritic cells revealed that an antagonist peptide induces translocation of the MTOC, and that this process is impaired in T cells from Fyn(-/-) OT-I mice. In addition, Fyn deficiency significantly affects the MTOC relocation mediated by agonist peptide stimulation. These results reveal Fyn to be a key regulator of tubulin cytoskeleton reorganization in T cells.
Martín-Cófreces
Noa B
NB
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
Sancho
David
D
Fernández
Edgar
E
Vicente-Manzanares
Miguel
M
Gordón-Alonso
Mónica
M
Montoya
María C
MC
Michel
Frédérique
F
Acuto
Oreste
O
Alarcón
Balbino
B
Sánchez-Madrid
Francisco
F
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D051076:Proto-Oncogene Proteins c-fyn / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C402726:Sh2d2a protein, mouse; D014404:Tubulin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn