ArticleNature communications2024
Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A two-step clockwork mechanism opens a proteo-lipidic pore in PIEZO2.Nature chemical biology · 2026Article
- LPA/LPAR signaling drives temporomandibular disorders-like pain through regulating the expression and sensitization of PIEZO2.Science advances · 2026Article
- Dynamic neutrophil lipidome remodeling during induction of NETosis.Science advances · 2026Article
- Cardiovascular PIEZO discovery continues apace to reveal myocardial nerves feeling posture and blood loss.Nature cardiovascular research · 2026Article
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026Review
- The interplay between extracellular matrix remodeling and cellular lipid metabolic reprogramming in cancer: a review.Molecular biology reports · 2025Review
- PIEZO2 in tumors: from mechanobiological switches to activity-targeted therapies.Journal of experimental & clinical cancer research : CR · 2025Review
- The research progress into cellular mechanosensitive ion channels mediating cancer pain.Channels (Austin, Tex.) · 2025Review
- Corneal Sensory Receptors and Pharmacological Therapies to Modulate Ocular Pain.International journal of molecular sciences · 2025Review
- Delayed-Onset Muscle Soreness Begins with a Transient Neural Switch.International journal of molecular sciences · 2025Review
- Pharmacology of PIEZO1 channels.British journal of pharmacology · 2024Review
- Proton-Mediated PIEZO2 Channelopathy: Linking Oxaliplatin Treatment to Impaired Proprioception and Cognitive Deficits.Cancers · 2024Article
- Transcriptomic analysis and high throughput functional characterization of human induced pluripotent stem cell derived sensory neurons.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Mechanosensitive PIEZO2 ion channels play roles in touch, proprioception, and inflammatory pain. Currently, there are no small molecule inhibitors that selectively inhibit PIEZO2 over PIEZO1. The TMEM120A protein was shown to inhibit PIEZO2 while leaving PIEZO1 unaffected. Here we find that TMEM120A expression elevates cellular levels of phosphatidic acid and lysophosphatidic acid (LPA), aligning with its structural resemblance to lipid-modifying enzymes. Intracellular application of phosphatidic acid or LPA inhibits PIEZO2 but not PIEZO1 activity. Extended extracellular exposure to the non-hydrolyzable phosphatidic acid and LPA analog carbocyclic phosphatidic acid (ccPA) also inhibits PIEZO2. Optogenetic activation of phospholipase D (PLD), a signaling enzyme that generates phosphatidic acid, inhibits PIEZO2 but not PIEZO1. Conversely, inhibiting PLD leads to increased PIEZO2 activity and increased mechanical sensitivity in mice in behavioral experiments. These findings unveil lipid regulators that selectively target PIEZO2 over PIEZO1, and identify the PLD pathway as a regulator of PIEZO2 activity.
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Registered trials
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.