ArticleProceedings of the National Academy of Sciences of the United States of America2019
Structure-guided examination of the mechanogating mechanism of PIEZO2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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.
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.
Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Roles of Piezo channels in dentofacial deformity: Onset, orthodontic treatment, and associated diseases.Genes & diseases · 2026Review
- Piezo channels in physical field therapy: From mechanotransduction mechanisms to bioelectromagnetic modulation and biomedical applications.Mechanobiology in medicine · 2026Review
- State-dependent binding of the wedge domain controls inactivation of the mechanosensitive ion channel PIEZO1.Nature communications · 2026Article
- Article
- Structures of invertebrate PEZO-1 isoforms with a compact architecture and a dispensable pore-distal N-terminal blade.Cell reports · 2026Article
- Targeting Piezo1/2 ion channels for modulation of the lymphatic system: mechanisms, applications, and therapeutic prospects.Burns & trauma · 2026Review
- Brain heart crosstalk after ischemic stroke toward a unified framework for pathophysiology and precision medicine.Frontiers in molecular neuroscience · 2026Review
- 3D-MINFLUX nanoscopy reveals distinct allosteric mechanisms for activation and modulation of PIEZO1 by Yoda1.Nature communications · 2025Article
- Cluster nanoarchitecture and structural diversity of PIEZO1 at rest and during activation in intact cells.Science advances · 2025Article
- The mechanobiology of biomolecular condensates.Biophysics reviews · 2025Review
- Computation suggests that the cell adhesion sub-proteome is enriched for sites of pH-dependence and charge burial.PloS one · 2025Article
- The activation thresholds and inactivation kinetics of poking-evoked PIEZO1 and PIEZO2 currents are sensitive to subtle variations in mechanical stimulation parameters.Channels (Austin, Tex.) · 2024Article
- Piezo ion channels: long-sought-after mechanosensors mediating hypertension and hypertensive nephropathy.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Ion channels in osteoarthritis: emerging roles and potential targets.Nature reviews. Rheumatology · 2024Review
- Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Emerging role of extracellular vesicles and exogenous stimuli in molecular mechanisms of peripheral nerve regeneration.Frontiers in cellular neuroscience · 2024Review
- Stretchable piezoelectric biocrystal thin films.Nature communications · 2023Article
- Mechanisms of PIEZO Channel Inactivation.International journal of molecular sciences · 2023Review
- The Janus-faced role of Piezo1 in cardiovascular health under mechanical stimulation.Genes & diseases · 2023Review
- Deciphering mechanically activated ion channels at the single-channel level in dorsal root ganglion neurons.The Journal of general physiology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Piezo channels are mechanically activated ion channels that confer mechanosensitivity to a variety of different cell types. Piezos oligomerize as propeller-shaped homotrimers that are thought to locally curve the membrane into spherical domes that project into the cell. While several studies have identified domains and amino acids that control important properties such as ion permeability and selectivity as well as inactivation kinetics and voltage sensitivity, only little is known about intraprotein interactions that govern mechanosensitivity-the most unique feature of PIEZOs. Here we used site-directed mutagenesis and patch-clamp recordings to investigate the mechanogating mechanism of PIEZO2. We demonstrate that charged amino acids at the interface between the beam domain-i.e., a long α-helix that protrudes from the intracellular side of the "propeller" blade toward the inner vestibule of the channel-and the C-terminal domain (CTD) as well as hydrophobic interactions between the highly conserved Y2807 of the CTD and pore-lining helices are required to ensure normal mechanosensitivity of PIEZO2. Moreover, single-channel recordings indicate that a previously unrecognized intrinsically disordered domain located adjacent to the beam acts as a cytosolic plug that limits ion permeation possibly by clogging the inner vestibule of both PIEZO1 and PIEZO2. Thus, we have identified several intraprotein domain interfaces that control the mechanical activation of PIEZO1 and PIEZO2 and which might thus serve as promising targets for drugs that modulate the mechanosensitivity of Piezo channels.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.