Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse

• Published in: Nature cell biology Vol. 11; no. 11; pp. 1332 - 1339
• Main Authors: Giacomello, Emiliana, Finetti, Francesca, Riparbelli, Maria Giovanna, Rosenbaum, Joel L, Paccani, Silvia Rossi, Pazour, Gregory J, Baldari, Cosima T, Perinetti, Giuseppe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2009; Nature Publishing Group
• Subjects: Antibodies; Antigen receptors, T cell; Antigens; Biological Transport; Biology; Biomedical and Life Sciences; Bone marrow; Cancer Research; Carrier Proteins - genetics; Carrier Proteins - immunology; CD3 Complex - immunology; CD3 Complex - metabolism; Cell Biology; Cellular signal transduction; Dendritic cells; Developmental Biology; Flagella - immunology; Flagella - metabolism; Gene Knockdown Techniques; Humans; Immunological Synapses - immunology; Immunological Synapses - metabolism; letter; Life Sciences; Localization; Lymphatic system; Lymphocytes; Physiological aspects; Receptors; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Stem Cells; Synapses; T cells; Thymus gland; United States; Italy; United States > US
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb1977

Most eukaryotic cells have a primary cilium which functions as a sensory organelle. Cilia are assembled by intraflagellar transport (IFT), a process mediated by multimeric IFT particles and molecular motors. Here we show that lymphoid and myeloid cells, which lack primary cilia, express IFT proteins. IFT20, an IFT component essential for ciliary assembly, was found to colocalize with both the microtubule organizing centre (MTOC) and Golgi and post-Golgi compartments in T-lymphocytes. In antigen-specific conjugates, IFT20 translocated to the immune synapse. IFT20 knockdown resulted in impaired T-cell receptor/CD3 (TCR/CD3) clustering and signalling at the immune synapse, due to defective polarized recycling. Moreover, IFT20 was required for the inducible assembly of a complex with other IFT components (IFT57 and IFT88) and the TCR. The results identify IFT20 as a new regulator of immune synapse assembly in T cells and provide the first evidence to implicate IFT in membrane trafficking in cells lacking primary cilia, thereby introducing a new perspective on IFT function beyond its role in ciliogenesis.