Summary of project PR001919
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001919. The data can be accessed directly via it's Project DOI: 10.21228/M8P13K This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001919 |
| Project DOI: | doi: 10.21228/M8P13K |
| Project Title: | Phospholipase D regulates PIEZO2 channels via formation of phosphatidic acid |
| Project Type: | Primary research |
| Project Summary: | 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 inhibited PIEZO2, but not PIEZO1 activity. Extended extracellular exposure to the non-hydrolyzable phosphatidic acid and LPA analogue carbocyclic phosphatidic acid (ccPA) also inhibited PIEZO2. Optogenetic activation of phospholipase D (PLD), responsible for phosphatidic acid generation, inhibited PIEZO2, but not PIEZO1. Conversely, inhibiting PLD led 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. |
| Institute: | Rutgers University |
| Department: | Pharmacology, Physiology and Neuroscience; Metabolomics Shared Resource |
| Laboratory: | Tibor Rohacs; Xiaoyang Su |
| Last Name: | Rohacs |
| First Name: | Tibor |
| Address: | 183 South Orange Ave, Newark, NJ, 07103 |
| Email: | rohacsti@njms.rutgers.edu |
| Phone: | 973-972-4464 |
| Funding Source: | NIH-NINDS R01-NS055159 to T.R.; NCI-CCSG P30CA072720-5923 to the Rutgers Cancer Institute of New Jersey Metabolomics Shared Resource |
| Contributors: | Matthew Gabrielle; Yevgen Yudin; Yujue Wang; Xiaoyang Su; Tibor Rohacs |
Summary of all studies in project PR001919
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003090 | Analysis of lipid profiles of N2A-Pz1-KO cells expressing tdTOMATO-vector (mock), TMEM120A, or TMEM120B | Mus musculus | Rutgers University | MS | 2024-07-16 | 1 | 9 | Uploaded data (662.5M)* |
