The molecular adapter Carma1 controls entry of IkappaB kinase into the central immune synapse.
Carma1 (also known as caspase recruitment domain [CARD]11, Bimp3) is a CARD-containing membrane-associated guanylate kinase family protein that plays an essential role in antigen receptor-induced nuclear factor kappaB activation. We investigated the role of Carma1 in the assembly of signaling molecules at the immune synapse using a peptide-specific system. We report that Carma1 is essential for peptide-induced interleukin 2 and interferon gamma production, but dispensable for proliferation in T cells. Recruitment and distribution of T cell receptor, lymphocyte function associated 1, lipid rafts, and protein kinase C (PKC)theta; to central and peripheral immune synapse regions occur normally in Carma1-/- T cells. Carma1 controls entry of IkappaB kinase (IKK) into lipid raft aggregates and the central region of the immune synapse, as well as activation of IKK downstream of PKC. Our data provide the first genetic evidence on a new class of molecular scaffold that controls entry of defined signaling components, IKK, into the central supramolecular activation cluster at T cell-antigen-presenting cell interfaces without having any apparent effect on the overall organization and formation of immune synapses.
Hara
Hiromitsu
H
IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, c/o Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria.
Bakal
Christopher
C
Wada
Teiji
T
Bouchard
Denis
D
Rottapel
Robert
R
Saito
Takashi
T
Penninger
Josef M
JM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002458:Cell Fractionation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051528:Guanylate Kinases; D051550:I-kappa B Kinase; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009703:Nucleoside-Phosphate Kinase / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D011493:Protein Kinase C; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases