Evidence map›Paper›PMID 20194498›Full record

ArticleThe Journal of biological chemistry2010

T cell signal regulation by the actin cytoskeleton.

Gurunadh R Chichili, Andrew D Westmuckett, William Rodgers

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
7.7field-weighted citation impact, top 3% 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

19 citing papers in PubMed, 35 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Gurunadh R ChichiliCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Andrew D Westmuckett
William Rodgers
Oklahoma Medical Research Foundation · USUniversity of Oklahoma Health Sciences Center · US

Funding

GEM Domains and T cell signalingR01GM070001 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI RODGERS, WILLIAM A · 2003 to 2007
$1.3M
NIGMS NIH HHS R01 GM070001
6 · The paper itself

Abstract

T cells form an immunological synapse (IS) that sustains and regulates signals for cell stimulation. Enriched in the IS is the Src family kinase Lck. Conversely, the membrane phosphatase CD45, which activates Src family kinases, is excluded, and this is necessary to avoid quenching of T cell receptor phosphosignals. Data suggest that this arrangement occurs by an enrichment of cholesterol-dependent rafts in the IS. However, the role of rafts in structuring the IS remains unclear. To address this question, we used fluorescence resonance energy transfer (FRET) to interrogate the nanoscopic structure of the IS. The FRET probes consisted of membrane-anchored fluorescent proteins with distinct affinities for rafts. Both the raft and nonraft probes exhibited clustering in the IS. However, co-clustering of raft donor-acceptor pairs was 10-fold greater than co-clustering of raft-nonraft pairs. We measured the effect of disrupting rafts in the IS on CD45 localization and Lck regulation by treating stimulated T cells with filipin. The filipin specifically disrupted co-clustering of the raft FRET pairs in the IS and allowed targeting of CD45 to the IS and dephosphorylation of the regulatory tyrosine of Lck. Clustering of the raft probes was also sensitive to latrunctulin B, which disrupts actin filaments. Strikingly, enriching the cortical cytoskeleton using jasplakinolide maintained raft probe co-clustering, CD45 exclusion, and Lck regulation in the IS following the addition of filipin. These data show the actin cytoskeleton maintains a membrane raft environment in the IS that promotes Lck regulation by excluding CD45.

Indexed as

ActinsAntineoplastic AgentsCholesterolCytoskeletonDepsipeptidesFilipinFluorescence Resonance Energy TransferHumansImmunological SynapsesJurkat CellsLeukocyte Common AntigensLymphocyte ActivationLymphocyte Specific Protein Tyrosine Kinase p56(lck)Membrane MicrodomainsReceptors, Antigen, T-CellT-LymphocytesActinsAntineoplastic AgentsCholesterolDepsipeptidesFilipinjasplakinolideLeukocyte Common AntigensLymphocyte Specific Protein Tyrosine Kinase p56(lck)Receptors, Antigen, T-CellTyrosine

Identifiers

PMID20194498
PMCPMC2863167
OpenAlexW2033820909

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.