Evidence map›Paper›PMID 39932556›Full record

ArticleThe Journal of cell biology2025

Single-molecule lipid biosensors mitigate inhibition of endogenous effector proteins.

Victoria L Holmes, Morgan M C Ricci, Claire C Weckerly, Michael Worcester, Gerald R V Hammond

Abstract read
In one paragraph

Article in The Journal of cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Quantitative comparison of PI(3,5)PMolecular biology of the cell · 2026
    Article
  2. Article
  3. Article
  4. Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026
    Review
  5. Quantitative comparison of PI(3,5)PbioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Victoria L Holmes *Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0009-0001-7680-5337
Morgan M C Ricci *Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-3705-5668
Claire C WeckerlyDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-2368-8429
Michael WorcesterDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0009-0009-9681-6875
Gerald R V HammondDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-6660-3272

Funding

Directing Membrane Function with Inositol Lipids in Health and DiseaseR35GM119412 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Gerald R Hammond · 2016 to 2026
$4.3M
NIGMS NIH HHS 2R35GM119412NIGMS NIH HHS R35 GM119412
6 · The paper itself

Abstract

Genetically encoded lipid biosensors uniquely provide real time, spatially resolved kinetic data for lipid dynamics in living cells. Despite clear strengths, these tools have significant drawbacks; most notably, lipid molecules bound to biosensors cannot engage with effectors, potentially inhibiting signaling. Here, we show that although PI 3-kinase (PI3K)-mediated activation of AKT is not significantly reduced in a cell population transfected with a PH-AKT1 PIP3/PI(3,4)P2 biosensor, single cells expressing PH-AKT at visible levels have reduced activation. Tagging endogenous AKT1 with neonGreen reveals its EGF-mediated translocation to the plasma membrane. Co-transfection with the PH-AKT1 or other PIP3 biosensors eliminates this translocation, despite robust recruitment of the biosensors. Inhibition is even observed with PI(3,4)P2-selective biosensor. However, expressing lipid biosensors at low levels, comparable with those of endogenous AKT, produced no such inhibition. Helpfully, these single-molecule biosensors revealed improved dynamic range and kinetic fidelity compared with overexpressed biosensor. This approach represents a noninvasive way to probe spatiotemporal dynamics of PI3K signaling in living cells.

Indexed as

Biosensing TechniquesLipidsProto-Oncogene Proteins c-aktSingle Molecule ImagingCell MembraneHEK293 CellsHumansPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesSignal TransductionAKT1 protein, humanLipidsphosphatidylinositol 3,4-diphosphatePhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesProto-Oncogene Proteins c-akt

Identifiers

PMID39932556
PMCPMC11812570

What OpenQuestion holds

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LicenceCC BY
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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.