Evidence map›Paper›PMID 34433665›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Lipid-based and protein-based interactions synergize transmembrane signaling stimulated by antigen clustering of IgE receptors.

Nirmalya Bag, Alice Wagenknecht-Wiesner, Allan Lee, Sophia M Shi, David A Holowka, Barbara A Baird

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 47 citations in OpenAlex.

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  11. Clustering of Membrane Receptors: Insights from DNA Origami-Based Approaches.Small (Weinheim an der Bergstrasse, Germany) · 2025
    Review
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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

6 authors at 1 institution in 1 country.

Nirmalya BagDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853 bab13@cornell.edu nb559@cornell.edu.ORCID 0000-0001-6752-9142
Alice Wagenknecht-WiesnerDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853.
Allan LeeDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853.
Sophia M ShiDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853.
David A HolowkaDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853.
Barbara A BairdDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853 bab13@cornell.edu nb559@cornell.edu.ORCID 0000-0003-0151-7899
Cornell University · US

Funding

High Resolution Characterization of Receptor Signaling and RegulationR01GM117552 · NIGMS · CORNELL UNIVERSITY · PI BAIRD, BARBARA A, HOLOWKA, DAVID A · 2016 to 2023
$3.2M
NIGMS NIH HHS R01 GM117552
6 · The paper itself

Abstract

Antigen (Ag) crosslinking of immunoglobulin E-receptor (IgE-FcεRI) complexes in mast cells stimulates transmembrane (TM) signaling, requiring phosphorylation of the clustered FcεRI by lipid-anchored Lyn tyrosine kinase. Previous studies showed that this stimulated coupling between Lyn and FcεRI occurs in liquid ordered (Lo)-like nanodomains of the plasma membrane and that Lyn binds directly to cytosolic segments of FcεRI that it initially phosphorylates for amplified activity. Net phosphorylation above a nonfunctional threshold is achieved in the stimulated state but not in the resting state, and current evidence supports the hypothesis that this relies on Ag crosslinking to disrupt a balance between Lyn and tyrosine phosphatase activities. However, the structural interactions that underlie the stimulation process remain poorly defined. This study evaluates the relative contributions and functional importance of different types of interactions leading to suprathreshold phosphorylation of Ag-crosslinked IgE-FcεRI in live rat basophilic leukemia mast cells. Our high-precision diffusion measurements by imaging fluorescence correlation spectroscopy on multiple structural variants of Lyn and other lipid-anchored probes confirm subtle, stimulated stabilization of the Lo-like nanodomains in the membrane inner leaflet and concomitant sharpening of segregation from liquid disordered (Ld)-like regions. With other structural variants, we determine that lipid-based interactions are essential for access by Lyn, leading to phosphorylation of and protein-based binding to clustered FcεRI. By contrast, TM tyrosine phosphatase, PTPα, is excluded from these regions due to its Ld-preference and steric exclusion of TM segments. Overall, we establish a synergy of lipid-based, protein-based, and steric interactions underlying functional TM signaling in mast cells.

Indexed as

Signal TransductionAnimalsAntigensCell Line, TumorCell MembraneCells, CulturedCHO CellsCricetulusGreen Fluorescent ProteinsLipid MetabolismLipidsMast CellsNanostructuresRatsReceptors, IgEsrc-Family KinasesAntigensGreen Fluorescent ProteinsLipidslyn protein-tyrosine kinaseReceptors, IgEsrc-Family KinasesFcεRIImaging FCSplasma membrane domainsraftstransmembrane signaling

Identifiers

PMID34433665
PMCPMC8536334
OpenAlexW3193575480

What Socratic 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 Socratic graph.