Evidence map›Paper›PMID 40923975›Full record

ArticleThe Journal of cell biology2025

PILS-Nir1 is a sensitive phosphatidic acid biosensor that reveals mechanisms of lipid production.

Claire C Weckerly, Taylor A Rahn, Max Ehrlich, Rachel C Wills, Joshua G Pemberton, Michael V Airola, 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. Review
  2. Article
  3. bioRxiv : the preprint server for biology · 2026
    Article
  4. Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026
    Review
  5. Article
  6. Article
  7. Nir2 crystal structures reveal a phosphatidic acid-sensing mechanism at ER-PM contact sites.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Claire C Weckerly *Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-2368-8429
Taylor A Rahn *Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.ORCID 0000-0002-5031-6914
Max EhrlichDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0009-0007-1168-5905
Rachel C WillsDepartment of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-2161-9235
Joshua G PembertonSection on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-1492-1471
Michael V AirolaDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.ORCID 0000-0003-4981-1253
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
Structure and regulation of lipid metabolism and transportR35GM128666 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI Michael Virgil Airola · 2018 to 2026
$4.0M
The roles of PLD and DGK isoforms in PIP2 homeostasis during PLC signalingF31HL170755 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WECKERLY, CLAIRE · 2023 to 2025
$126k
NHLBI NIH HHS F31 HL170755NIGMS NIH HHS R35 GM119412NIGMS NIH HHS R35 GM128666NIH HHS 1F31HL170755-01NIH HHS R35GM119412NIH HHS R35GM12866Sloan Research Foundation
6 · The paper itself

Abstract

Phosphatidic acid (PA) regulates lipid homeostasis and vesicular trafficking, yet high-affinity tools to study PA in live cells are lacking. We identified the lipin-like sequence of Nir1 (PILS-Nir1) as a candidate PA biosensor based on structural analysis of Nir1's LNS2 domain. Using liposome-binding assays and pharmacological and genetic manipulations in HEK293A cells expressing fluorescent PILS-Nir1, we found that while PILS-Nir1 binds PA and PIP2in vitro, only PA is necessary and sufficient for membrane localization in cells. PILS-Nir1 displayed greater sensitivity to organelle-generated PA than Spo20-based probes, enabling visualization of modest PA production by PLD downstream of muscarinic receptors-previously undetectable with existing biosensors. Thus, PILS-Nir1 provides a versatile, sensitive tool for real-time PA dynamics in live cells.

Indexed as

Biosensing TechniquesLipid MetabolismPhosphatidic AcidsHEK293 CellsHumansLiposomesLiposomesPhosphatidic Acids

Identifiers

PMID40923975
PMCPMC12419160

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.