Abstract
T cell receptor (TCR)-mediated cytoskeletal reorganization is considered to be actin-related protein (Arp) 2/3 complex dependent. We therefore examined the requirement for Arp2/3- and formin-dependent F-actin nucleation during T cell activation. We demonstrated that without Arp2/3-mediated actin nucleation, stimulated T cells could not form an F-actin-rich lamellipod, but instead produced polarized filopodia-like structures. Moreover, the microtubule-organizing center (MTOC, or centrosome), which rapidly reorients to the immunological synapse through an unknown mechanism, polarized in the absence of Arp2/3. Conversely, the actin-nucleating formins, Diaphanous-1 (DIA1) and Formin-like-1 (FMNL1), did not affect TCR-stimulated F-actin-rich structures, but instead displayed unique patterns of centrosome colocalization and controlled TCR-mediated centrosome polarization. Depletion of FMNL1 or DIA1 in cytotoxic lymphocytes abrogated cell-mediated killing. Altogether, our results have identifed Arp2/3 complex-independent cytoskeletal reorganization events in T lymphocytes and indicate that formins are essential cytoskeletal regulators of centrosome polarity in T cells.
Original language | English (US) |
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Pages (from-to) | 177-190 |
Number of pages | 14 |
Journal | Immunity |
Volume | 26 |
Issue number | 2 |
DOIs | |
State | Published - Feb 23 2007 |
Bibliographical note
Funding Information:We would like to thank R.A. Schoon and C.J. Dick for their help with the cytotoxicity assays. This work was supported by the Mayo Foundation, NIH grant R01-AI065474 to D.D.B., NIH grant F31-AI068624 to T.S.G., NIH grant R01-CA47752 to P.J.L., and NIH grants R01-AI038474 and R01-AI031126 to Y.S. The authors declare that they have no competing financial interests.
Keywords
- CELLBIO
- MOLIMMUNO