Evidence map›Paper›PMID 40309905›Full record

ArticleeLife2025

ATP-release pannexin channels are gated by lysophospholipids.

Erik Henze, Russell N Burkhardt, Bennett William Fox, Tyler J Schwertfeger, Eric Gelsleichter, Kevin Michalski, Lydia Kramer, Margret Lenfest, Jordyn M Boesch, Hening Lin and 2 more

Abstract read
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. The C-terminal activating domain promotes pannexin 1 channel opening.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. The C-terminal activating domain promotes Panx1 channel opening.bioRxiv : the preprint server for biology · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Erik HenzeDepartment of Molecular Medicine, Cornell University, Ithaca, United States.
Russell N BurkhardtBoyce Thompson Institute, Cornell University, Ithaca, United States.
Bennett William FoxBoyce Thompson Institute, Cornell University, Ithaca, United States.
Tyler J SchwertfegerBoyce Thompson Institute, Cornell University, Ithaca, United States.
Eric GelsleichterDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, United States.
Kevin MichalskiDepartment of Molecular Medicine, Cornell University, Ithaca, United States.
Lydia KramerDepartment of Molecular Medicine, Cornell University, Ithaca, United States.
Margret LenfestDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United States.
Jordyn M BoeschDepartment of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United States.ORCID https://orcid.org/0000-0002-2032-1202
Hening LinDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, United States.ORCID https://orcid.org/0000-0002-0255-2701
Frank C SchroederBoyce Thompson Institute, Cornell University, Ithaca, United States.
Toshimitsu KawateDepartment of Molecular Medicine, Cornell University, Ithaca, United States.ORCID https://orcid.org/0000-0002-5005-2031

Funding

TRAINING IN MOLECULAR PHYSICS OF BIOLOGICAL SYSTEMST32GM008267 · NIGMS · CORNELL UNIVERSITY ITHACA · PI WANG, MICHELLE D. · 1988 to 2021
$9.6M
Small molecule signaling in C. elegansR35GM131877 · NIGMS · BOYCE THOMPSON INST FOR PLANT RESEARCH · PI Frank Clemens Schroeder · 2019 to 2026
$5.0M
The role of AEG-1 in NASH and NASH-HCCR01DK107451 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI SARKAR, DEVANAND · 2016 to 2025
$3.9M
Structure and Function of Pannexins: Activation MechanismR01GM114379 · NIGMS · CORNELL UNIVERSITY · PI KAWATE, TOSHIMITSU · 2015 to 2025
$3.1M
National Science Foundation DBI1659534NIDDK NIH HHS R01 DK107451NIGMS NIH HHS R01 GM114379NIGMS NIH HHS R35 GM131877NIGMS NIH HHS T32 GM008267NIH HHS R01DK107451NIH HHS R01GM114379NIH HHS R35GM131877NIH HHS T32GM008267
6 · The paper itself

Abstract

In addition to its role as cellular energy currency, adenosine triphosphate (ATP) serves as an extracellular messenger that mediates diverse cell-to-cell communication. Compelling evidence supports that ATP is released from cells through pannexins, a family of membrane proteins that form heptameric large-pore channels. However, the activation mechanisms that trigger ATP release by pannexins remain poorly understood. Here, we discover lysophospholipids as endogenous pannexin activators, using activity-guided fractionation of mouse tissue extracts combined with untargeted metabolomics and electrophysiology. We show that lysophospholipids directly and reversibly activate pannexins in the absence of other proteins. Secretomics experiments reveal that lysophospholipid-activated pannexin 1 leads to the release of not only ATP but also other signaling metabolites, such as 5'-methylthioadenosine, which is important for immunomodulation. We also demonstrate that lysophospholipids activate endogenous pannexin 1 in human monocytes, leading to the release of IL-1β through inflammasome activation. Our results provide a connection between lipid metabolism and purinergic signaling, both of which play major roles in immune responses.

Indexed as

Adenosine TriphosphateConnexinsLysophospholipidsNerve Tissue ProteinsAnimalsHumansInterleukin-1betaMiceMice, Inbred C57BLMonocytesAdenosine TriphosphateConnexinsInterleukin-1betaLysophospholipidsNerve Tissue ProteinsPANX1 protein, humanPanx1 protein, mousehumaninflammasomelarge pore channellipid signalingmolecular biophysicssecretomicsstructural biologyuntargeted metabolomicsxenopus

Identifiers

PMID40309905
PMCPMC12045621

What Socratic 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 Socratic graph.