Formins Regulate the Actin-Related Protein 2/3 Complex-Independent Polarization of the Centrosome to the Immunological Synapse

Timothy S. Gomez, Karan Kumar, Ricardo B. Medeiros, Yoji Shimizu, Paul J. Leibson, Daniel D D. Billadeau

Research output: Contribution to journalArticlepeer-review

221 Scopus citations

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 languageEnglish (US)
Pages (from-to)177-190
Number of pages14
JournalImmunity
Volume26
Issue number2
DOIs
StatePublished - 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

Fingerprint

Dive into the research topics of 'Formins Regulate the Actin-Related Protein 2/3 Complex-Independent Polarization of the Centrosome to the Immunological Synapse'. Together they form a unique fingerprint.

Cite this