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 journalArticle

175 Citations (Scopus)

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

Fingerprint

Actin-Related Protein 2-3 Complex
Immunological Synapses
Centrosome
Actins
T-Cell Antigen Receptor
Microtubule-Organizing Center
T-Lymphocytes
Pseudopodia
Lymphocytes
formin 1

Keywords

  • CELLBIO
  • MOLIMMUNO

Cite this

Formins Regulate the Actin-Related Protein 2/3 Complex-Independent Polarization of the Centrosome to the Immunological Synapse. / Gomez, Timothy S.; Kumar, Karan; Medeiros, Ricardo B.; Shimizu, Yoji; Leibson, Paul J.; Billadeau, Daniel D D.

In: Immunity, Vol. 26, No. 2, 23.02.2007, p. 177-190.

Research output: Contribution to journalArticle

Gomez, Timothy S. ; Kumar, Karan ; Medeiros, Ricardo B. ; Shimizu, Yoji ; Leibson, Paul J. ; Billadeau, Daniel D D. / Formins Regulate the Actin-Related Protein 2/3 Complex-Independent Polarization of the Centrosome to the Immunological Synapse. In: Immunity. 2007 ; Vol. 26, No. 2. pp. 177-190.
@article{dd2cff0125a24af7b7a44bde40d8c3b1,
title = "Formins Regulate the Actin-Related Protein 2/3 Complex-Independent Polarization of the Centrosome to the Immunological Synapse",
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.",
keywords = "CELLBIO, MOLIMMUNO",
author = "Gomez, {Timothy S.} and Karan Kumar and Medeiros, {Ricardo B.} and Yoji Shimizu and Leibson, {Paul J.} and Billadeau, {Daniel D D.}",
year = "2007",
month = "2",
day = "23",
doi = "10.1016/j.immuni.2007.01.008",
language = "English (US)",
volume = "26",
pages = "177--190",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Formins Regulate the Actin-Related Protein 2/3 Complex-Independent Polarization of the Centrosome to the Immunological Synapse

AU - Gomez, Timothy S.

AU - Kumar, Karan

AU - Medeiros, Ricardo B.

AU - Shimizu, Yoji

AU - Leibson, Paul J.

AU - Billadeau, Daniel D D.

PY - 2007/2/23

Y1 - 2007/2/23

N2 - 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.

AB - 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.

KW - CELLBIO

KW - MOLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=33847311403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847311403&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2007.01.008

DO - 10.1016/j.immuni.2007.01.008

M3 - Article

C2 - 17306570

AN - SCOPUS:33847311403

VL - 26

SP - 177

EP - 190

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -