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Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility

Nature Cell Biology volume 11, pages 17–26 (2009)Cite this article

Abstract

The systems that refine actomyosin forces during motility remain poorly understood. Septins assemble on the T-cell cortex and are enriched at the mid-zone in filaments. Septin knockdown causes membrane blebbing, excess leading-edge protrusions and lengthening of the trailing-edge uropod. The associated loss of rigidity permits motility, but cells become uncoordinated and poorly persistent. This also relieves a previously unrecognized restriction to migration through small pores. Pharmacologically rigidifying cells counteracts this effect, and relieving cytoskeletal rigidity synergizes with septin depletion. These data suggest that septins tune actomyosin forces during motility and probably regulate lymphocyte trafficking in confined tissues.

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Figure 1: Septin complexes form in T cells, assemble on the cortex and form filaments and puncta in the mid-zone.
Figure 2: Septin knockdown in T cells results in augmented length and bending of uropods.
Figure 3: Septin complexes are required for structural stability of the cell cortex and at the T-cell mid-zone.
Figure 4: Integrity of tubulin and actomyosin cytoskeletons in septin-deficient T cells.
Figure 5: Septins regulate motility and transmigration.
Figure 6: Septins and microtubules regulate rigidity and transmigration.

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Acknowledgements

We thank A. Weiss and M.T. McManus for insight and critical discussions, ShuWei Jiang and Cliff McArthur for expert technical assistance with cell sorting and Christine Lin and Ed Shimazu for computer support. We also thank Cynthia Voong for critical reading of the manuscript and members of the Krummel lab for thoughtful discussions. This work was supported by the NIH(R21-AI062899), the Sandler family fund, the National Science Foundation and the Leukemia and Lymphoma Society.

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Author notes

  1. Aaron J. Tooley and Julia Gilden: These authors contributed equally to this work.

Authors and Affiliations

  1. The Department of Pathology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, 94143-0511, CA, USA

    Aaron J. Tooley, Julia Gilden, Jordan Jacobelli, Peter Beemiller & Matthew F. Krummel

  2. Hospital for Sick Children and Department of Biochemistry, Program in Cell Biology, University of Toronto, 555 University Avenue, Toronto, M5G 1X8, Canada

    William S. Trimble

  3. Biochemistry and Cell Biology Unit, HMRO, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo, 606-8501, Kyoto, Japan

    Makoto Kinoshita

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Contributions

J.G. and A.T. performed all experiments and wrote the manuscript; J.J. and P.B. assisted with the data analysis and planning the experiments; W.S.T. and M.K. contributed reagents and gave conceptual assistance; M.F.K. coordinated the project and assisted with planning the experiments and writing the manuscript. All authors discussed the results and manuscript text.

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Correspondence to Matthew F. Krummel.

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Tooley, A., Gilden, J., Jacobelli, J. et al. Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility. Nat Cell Biol 11, 17–26 (2009). https://doi.org/10.1038/ncb1808

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