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Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse.

Publication ,  Journal Article
Gomez, TS; Kumar, K; Medeiros, RB; Shimizu, Y; Leibson, PJ; Billadeau, DD
Published in: Immunity
February 2007

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 identified Arp2/3 complex-independent cytoskeletal reorganization events in T lymphocytes and indicate that formins are essential cytoskeletal regulators of centrosome polarity in T cells.

Duke Scholars

Published In

Immunity

DOI

ISSN

1074-7613

Publication Date

February 2007

Volume

26

Issue

2

Start / End Page

177 / 190

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes
  • Microscopy, Electron, Scanning
  • Lymphocyte Activation
  • Jurkat Cells
  • Immunoprecipitation
  • Immunology
  • Immunoblotting
  • Humans
  • Formins
 

Citation

APA
Chicago
ICMJE
MLA
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Gomez, T. S., Kumar, K., Medeiros, R. B., Shimizu, Y., Leibson, P. J., & Billadeau, D. D. (2007). Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity, 26(2), 177–190. https://doi.org/10.1016/j.immuni.2007.01.008
Gomez, Timothy S., Karan Kumar, Ricardo B. Medeiros, Yoji Shimizu, Paul J. Leibson, and Daniel D. Billadeau. “Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse.Immunity 26, no. 2 (February 2007): 177–90. https://doi.org/10.1016/j.immuni.2007.01.008.
Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD. Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity. 2007 Feb;26(2):177–90.
Gomez, Timothy S., et al. “Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse.Immunity, vol. 26, no. 2, Feb. 2007, pp. 177–90. Pubmed, doi:10.1016/j.immuni.2007.01.008.
Gomez TS, Kumar K, Medeiros RB, Shimizu Y, Leibson PJ, Billadeau DD. Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity. 2007 Feb;26(2):177–190.
Journal cover image

Published In

Immunity

DOI

ISSN

1074-7613

Publication Date

February 2007

Volume

26

Issue

2

Start / End Page

177 / 190

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes
  • Microscopy, Electron, Scanning
  • Lymphocyte Activation
  • Jurkat Cells
  • Immunoprecipitation
  • Immunology
  • Immunoblotting
  • Humans
  • Formins