Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.
Actin reorganization at the immunological synapse is required for the amplification and generation of a functional immune response. Using small interfering RNA, we show here that dynamin 2 (Dyn2), a large GTPase involved in receptor-mediated internalization, did not alter antibody-mediated T cell receptor internalization but considerably affected T cell receptor-stimulated T cell activation by regulating multiple biochemical signaling pathways and the accumulation of F-actin at the immunological synapse. Moreover, Dyn2 interacted directly with the Rho family guanine nucleotide exchange factor Vav1, and this interaction was required for T cell activation. These data identify a functionally important interaction between Dyn2 and Vav1 that regulates actin reorganization and multiple signaling pathways in T lymphocytes.
Gomez
Timothy S
TS
Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Hamann
Michael J
MJ
McCarney
Sean
S
Savoy
Doris N
DN
Lubking
Casey M
CM
Heldebrant
Michael P
MP
Labno
Christine M
CM
McKean
David J
DJ
McNiven
Mark A
MA
Burkhardt
Janis K
JK
Billadeau
Daniel D
DD
D000199:Actins / Q000378:metabolism*; D001483:Base Sequence; D001704:Biopolymers / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D034285:Dynamin II / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000199:Actins; D001704:Biopolymers; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496618:VAV1 protein, human; D034285:Dynamin II