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

Nature Cell Biology volume 11, pages 13321339 (2009) | Download Citation

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Abstract

Most eukaryotic cells have a primary cilium which functions as a sensory organelle1. Cilia are assembled by intraflagellar transport (IFT), a process mediated by multimeric IFT particles and molecular motors2. Here we show that lymphoid and myeloid cells, which lack primary cilia, express IFT proteins. IFT20, an IFT component essential for ciliary assembly3,4, 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.

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Acknowledgements

The authors want to thank G. Callaini for invaluable help with fluorescence microscopy, S. Grassini for technical assistance, A. Alcover, S. Valitutti, P. Lupetti, A. Luini, A. Colanzi, A. De Matteis and C. Mencarelli for useful discussions and J. L Telford and A. Alcover for critical reading of the manuscript. This work was supported by grants from AIRC (to C.T.B.) and the National Institutes of Health (GM060992 to G.J.P. and GM-14,642 to J.L.R.). F.F. is the recipient of a FIRC fellowship.

Author information

Affiliations

  1. Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.

    • Francesca Finetti
    • , Silvia Rossi Paccani
    • , Maria Giovanna Riparbelli
    •  & Cosima T. Baldari
  2. Department of Neuroscience, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.

    • Emiliana Giacomello
  3. Department of Biomedicine, University of Trieste, 34138 Trieste, Italy.

    • Giuseppe Perinetti
  4. Program in Molecular Medicine, University of Massachussetts Medical School, Worcester, MA 01605, USA.

    • Gregory J. Pazour
  5. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.

    • Joel L. Rosenbaum

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Contributions

F.F., S.R.P., C.T.B., G.J.P. and J.L.R. planned the project and drafted the manuscript; F.F., S.R.P., M.G.R. and E.G. carried out the experimental work; F.F., S.R.P., C.T.B., E.G., G.P. and M.G.R. analysed the data.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Cosima T. Baldari.

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DOI

https://doi.org/10.1038/ncb1977

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