Evidence map›Paper›PMID 34279667›Full record

ArticleJournal of cell science2021

LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors.

Keith P Eidell, Alenka Lovy, Nicholas R Sylvain, Frank A Scangarello, Hayley I Muendlein, Michael J Ophir, Ken Nguyen, Maria-Cristina Seminario, Stephen C Bunnell

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 42% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
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

9 authors at 1 institution in 1 country.

Keith P EidellGraduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.ORCID 0000-0002-5971-218X
Alenka LovyDepartment of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.ORCID 0000-0002-8167-3199
Nicholas R SylvainGraduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.ORCID 0000-0003-4325-1953
Frank A ScangarelloGraduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.ORCID 0000-0002-3993-608X
Hayley I MuendleinGraduate Program in Genetics, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.ORCID 0000-0003-3006-5780
Michael J OphirGraduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.ORCID 0000-0002-5516-1237
Ken NguyenGraduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.ORCID 0000-0002-3644-3490
Maria-Cristina SeminarioDepartment of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.ORCID 0000-0003-0762-8661
Stephen C BunnellDepartment of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.ORCID 0000-0001-6887-0828
Tufts University · US

Funding

TUSM/T-NEMC CENTER FOR NEUROSCIENCE RESEARCH - Imaging CoreP30NS047243 · NINDS · TUFTS UNIVERSITY BOSTON · PI JACKSON, F ROB · 2003 to 2017
$10.0M
MEDICAL SCIENTIST TRAINING PROGRAM AT TUFTS UNIVERSITYT32GM008448 · NIGMS · TUFTS UNIVERSITY BOSTON · PI CHIN, MICHAEL T · 1994 to 2022
$9.1M
IMMUNOLOGIC ASPECTS OF DISEASET32AI007077 · NIAID · TUFTS UNIVERSITY BOSTON · PI WORTIS, HENRY H. · 1985 to 2017
$3.5M
Mechanisms of Integrin-Mediated Costimulation in T CellsR01AI076575 · NIAID · TUFTS UNIVERSITY BOSTON · PI BUNNELL, STEPHEN C · 2009 to 2013
$1.9M
Age-related changes in the proteome and lipidome of the immunological synapseR21AG030931 · NIA · TUFTS UNIVERSITY BOSTON · PI MEYDANI, SIMIN NIKBIN · 2007 to 2008
$365k
American Heart Association-American Stroke Association 0635546TNIAID NIH HHS R01 AI076575NIAID NIH HHS T32 AI007077NIA NIH HHS R21 AG030931NIGMS NIH HHS T32 GM008448NIH HHS R01-AI076575NIH HHS R01 AI076575-01NINDS NIH HHS P30 NS047243
6 · The paper itself

Abstract

Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB1) and SKAP55 (SKAP1) are recruited into microclusters and activate integrins via the effectors talin-1 and kindlin-3 (FERMT3). We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages. We show that contractile myosin filaments surround and are co-transported with SLP-76 microclusters, and that TCR ligand density governs the centripetal movement of both structures. Centripetal transport requires formin activity, actomyosin contraction, microtubule integrity and dynein motor function. Although immobilized VLA-4 (α4β1 integrin) and LFA-1 (αLβ2 integrin) ligands arrest the centripetal movement of SLP-76 microclusters and myosin filaments, VLA-4 acts distally, while LFA-1 acts in the lamellum. Integrin β2, kindlin-3 and zyxin are required for complete centripetal transport, while integrin β1 and talin-1 are not. CD69 upregulation is similarly dependent on integrin β2, kindlin-3 and zyxin, but not talin-1. These findings highlight the integration of cytoskeletal systems within the immune synapse and reveal extracellular ligand-independent roles for LFA-1 and kindlin-3. This article has an associated First Person interview with the first author of the paper.

Indexed as

DyneinsLymphocyte Function-Associated Antigen-1Cell AdhesionHumansMembrane ProteinsMyosinsReceptors, Antigen, T-CellDyneinsLymphocyte Function-Associated Antigen-1Membrane ProteinsMyosinsReceptors, Antigen, T-CellImmune synapseIntegrinMicroclustersMyosinSLP-76T cell signaling

Identifiers

PMID34279667
PMCPMC8435290
OpenAlexW3183306615

What OpenQuestion holds

Textmetadata
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.