title: Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.
abstract: 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.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Gomez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hamann
authors.forename: Sean
authors.initials: S
authors.lastname: McCarney
authors.forename: Doris N
authors.initials: DN
authors.lastname: Savoy
authors.forename: Casey M
authors.initials: CM
authors.lastname: Lubking
authors.forename: Michael P
authors.initials: MP
authors.lastname: Heldebrant
authors.forename: Christine M
authors.initials: CM
authors.lastname: Labno
authors.forename: David J
authors.initials: DJ
authors.lastname: McKean
authors.forename: Mark A
authors.initials: MA
authors.lastname: McNiven
authors.forename: Janis K
authors.initials: JK
authors.lastname: Burkhardt
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Billadeau
mesh_terms: 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*
chemical_list: 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