Evidence map›Paper›PMID 22665519›Full record

ArticleThe Journal of cell biology2012

F-actin polymerization and retrograde flow drive sustained PLCγ1 signaling during T cell activation.

Alexander Babich, Shuixing Li, Roddy S O'Connor, Michael C Milone, Bruce D Freedman, Janis K Burkhardt

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

136 citing papers in PubMed, 202 citations in OpenAlex.

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  16. Mechanics of cell-cell junctions.Biophysical journal · 2023
    Article
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76 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Alexander BabichDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shuixing Li
Roddy S O'Connor
Michael C Milone
Bruce D Freedman
Janis K Burkhardt
University of Pennsylvania · USChildren's Hospital of Philadelphia · US

Funding

Nanomedicine development center for mechanobiologyPN2EY016586 · NEI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DUSTIN, MICHAEL LORAN · 2005 to 2014
$23.0M
The Function of Tribbles in the Pathogenesis of AMLP01CA093615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI BIRNBAUM, MORRIS J · 2002 to 2011
$16.2M
TRAINING PROGRAM/RHEUMATIC DISEASEST32AR007442 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI BEHRENS, EDWARD M, MERKEL, PETER A · 1986 to 2018
$5.8M
Novel Mechanisms of Calcium Signaling in B lymphocytesR01AI060921 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI FREEDMAN, BRUCE D · 2005 to 2014
$3.9M
Cytoskeletal Remodeling During T Cell ActivationR01AI065644 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BURKHARDT, JANIS K. · 2007 to 2011
$2.0M
NCI NIH HHS P01 CA093615NCI NIH HHS P01CA093615NEI NIH HHS PN2 EY016586NIAID NIH HHS R01 AI060921NIAID NIH HHS R01 AI065644NIAID NIH HHS R01AI065644NIAMS NIH HHS 5T32AR7442-25NIAMS NIH HHS T32 AR007442
6 · The paper itself

Abstract

Activation of T cells by antigen-presenting cells involves assembly of signaling molecules into dynamic microclusters (MCs) within a specialized membrane domain termed the immunological synapse (IS). Actin and myosin IIA localize to the IS, and depletion of F-actin abrogates MC movement and T cell activation. However, the mechanisms that coordinate actomyosin dynamics and T cell receptor signaling are poorly understood. Using pharmacological inhibitors that perturb individual aspects of actomyosin dynamics without disassembling the network, we demonstrate that F-actin polymerization is the primary driver of actin retrograde flow, whereas myosin IIA promotes long-term integrity of the IS. Disruption of F-actin retrograde flow, but not myosin IIA contraction, arrested MC centralization and inhibited sustained Ca(2+) signaling at the level of endoplasmic reticulum store release. Furthermore, perturbation of retrograde flow inhibited PLCγ1 phosphorylation within MCs but left Zap70 activity intact. These studies highlight the importance of ongoing actin polymerization as a central driver of actomyosin retrograde flow, MC centralization, and sustained Ca(2+) signaling.

Indexed as

Signal TransductionActinsCell MovementHumansJurkat CellsLymphocyte ActivationNonmuscle Myosin Type IIAPhospholipase C gammaPolymerizationReceptors, Antigen, T-CellT-LymphocytesTransfectionZAP-70 Protein-Tyrosine KinaseActinsNonmuscle Myosin Type IIAPhospholipase C gammaReceptors, Antigen, T-CellZAP70 protein, humanZAP-70 Protein-Tyrosine Kinase

Identifiers

PMID22665519
PMCPMC3373411
OpenAlexW2094476644

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.