Affinage

PIEZO2

Piezo-type mechanosensitive ion channel component 2 · UniProt Q9H5I5

Length
2752 aa
Mass
318.1 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIEZO2 is a rapidly adapting, mechanically activated non-selective cation channel that serves as the principal transducer converting physical force into electrical and calcium signals across diverse sensory and non-neuronal tissues (PMID:20813920, PMID:25471886). It is the major channel for discriminative touch and proprioception, acting in Merkel cells, low-threshold mechanoreceptors, and muscle-spindle/Golgi-tendon proprioceptors (PMID:24717433, PMID:25471886, PMID:26551544), with human loss-of-function mutations causing selective loss of touch and proprioception and gain-of-function mutations causing Distal Arthrogryposis Type 5 by altering channel inactivation kinetics (PMID:23487782, PMID:27653382). Beyond somatosensation, PIEZO2 mediates mechanotransduction in bladder urothelium and stretch-sensing neurons, enterochromaffin cells (driving serotonin release), and cochlear outer hair cells (PMID:30037999, PMID:33057202, PMID:34244441). Its mechanogating depends on defined structural elements: blade domains transmit force and confer cold sensitivity, a beam–CTD interface and pore-lining helix interactions (Y2807) set mechanosensitivity, an intrinsically disordered cytosolic plug limits ion permeation, and the IDR5 linker couples the channel to cytoskeleton-transmitted forces, establishing that distinct stimuli (indentation versus stretch) engage distinct force-transmission pathways (PMID:31413193, PMID:31235572, PMID:35292651). Channel output is tuned by extensive cell-type-specific alternative splicing, voltage-dependent block at resting potential, and inactivation kinetics that govern frequency filtering (PMID:29212024, PMID:28636944, PMID:38984717). Activity is sensitized by inflammatory and GPCR signaling cascades—PKA/PKC, Epac1-cAMP, and Gβγ–PI3K/MAPK—underlying mechanical allodynia and itch (PMID:22921401, PMID:23575686, PMID:32227462, PMID:36961815), and is regulated by lipids (inhibition by phosphatidic acid via PLD/TMEM120A and by PI(3,5)P2 depletion via Mtmr2) and by interacting proteins controlling its current amplitude, trafficking, and membrane expression (Nedd4-2, TMC7, EndoA2/KIF5B, Pericentrin) (PMID:29521261, PMID:35819364, PMID:39147733, PMID:38568807, PMID:38475827). PIEZO2-driven calcium influx also couples to downstream cytoskeletal and transcriptional programs, including a RhoA/YAP axis in cancer cell invasion (PMID:29432180).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2010 High

    Established PIEZO2 as a bona fide component of mechanically activated channels, answering whether a discrete molecule underlies rapidly adapting touch currents.

    Evidence RNAi knockdown plus heterologous overexpression with patch-clamp in DRG neurons

    PMID:20813920

    Open questions at the time
    • Did not establish whether PIEZO2 is the pore-forming subunit versus an accessory component
    • No structural or domain-level mechanism of gating
  2. 2013 High

    Linked PIEZO2 to human disease by showing gain-of-function mutations alter inactivation kinetics, connecting channel biophysics to Distal Arthrogryposis Type 5.

    Evidence Patch-clamp of mutant channels and whole-exome sequencing

    PMID:23487782

    Open questions at the time
    • Did not resolve the structural basis of inactivation
    • Tissue-level mechanism connecting altered gating to joint contracture not defined
  3. 2013 High

    Defined inflammatory and intracellular signaling sensitization of PIEZO2, addressing how the channel becomes hyperactive in pain states.

    Evidence Pharmacological PKA/PKC and Epac manipulation, GTP substitution, electrophysiology, and in vivo knockdown with behavior

    PMID:22921401 PMID:23575686 PMID:24344923

    Open questions at the time
    • Direct phosphorylation sites not yet mapped
    • Molecular identity of GTP-dependent regulator unknown
  4. 2014 High

    Identified PIEZO2 as the in vivo transducer for touch in Merkel cells and low-threshold mechanoreceptors, settling its physiological role in cutaneous sensation.

    Evidence Skin- and neuron-specific conditional knockout mice with DRG/skin-nerve electrophysiology, in vivo recordings, and behavior; CRISPR deletion in human stem-cell-derived neurons

    PMID:24717433 PMID:25469543 PMID:25471886

    Open questions at the time
    • Residual non-PIEZO2 mechanotransduction in some afferents not explained
    • Cell-type specificity of channel properties not addressed
  5. 2015 High

    Established PIEZO2 as the principal proprioceptive channel, answering how body position is mechanically sensed.

    Evidence Two independent proprioceptor-specific knockout mouse lines with muscle-nerve recordings and behavior

    PMID:26551544 PMID:27184818

    Open questions at the time
    • How force from muscle spindles reaches the channel not defined
    • Contribution of accessory structures to gating unknown
  6. 2016 High

    Confirmed PIEZO2 as a determinant of human mechanosensation, showing loss-of-function selectively impairs discriminative touch and proprioception.

    Evidence Whole-exome sequencing with functional assays, brain imaging, and psychophysical testing

    PMID:27653382

    Open questions at the time
    • Did not address non-somatosensory roles later found in bladder, gut, and hearing
  7. 2016 High

    Identified native PIEZO2 regulators, revealing how lipids and accessory proteins tune mechanically activated currents.

    Evidence Mass-spectrometry native interactomics with Co-IP, domain-swap mutants, and electrophysiology (Mtmr2/PI(3,5)P2; Pericentrin)

    PMID:27345391 PMID:29521261

    Open questions at the time
    • Pericentrin mechanism of modulation only partly resolved (Medium)
    • Whether lipid regulation operates in all PIEZO2-expressing tissues unknown
  8. 2017 High

    Showed that alternative splicing and inactivation kinetics diversify and filter PIEZO2 output, explaining tissue-specific channel behavior and frequency tuning.

    Evidence Isoform profiling and patch-clamp of splice variants and disease mutations with simulation

    PMID:28636944 PMID:29212024

    Open questions at the time
    • Functional consequences of specific isoforms in vivo not established
  9. 2019 High

    Defined the structural elements of mechanogating, addressing how force is transmitted to channel opening and ion permeation.

    Evidence Structure-guided mutagenesis with single-channel and whole-cell electrophysiology; domain swapping for cold sensitivity; single-channel biophysical characterization

    PMID:31015490 PMID:31235572 PMID:31413193

    Open questions at the time
    • High-resolution structure of gated states not provided in corpus
    • Curvature-sensitivity data from single cell type only (Medium)
  10. 2018 High

    Extended PIEZO2 function beyond somatosensation to gut and cancer, showing it drives enterochromaffin serotonin release and a RhoA/YAP invasion axis.

    Evidence Conditional KO, organoid Ca2+ imaging, serotonin ELISA; siRNA with RhoA activity assays and rescue in metastatic cells

    PMID:27392819 PMID:29432180 PMID:30037999

    Open questions at the time
    • Mechanical stimulus source in vivo for EC cells not fully defined
    • Generality of the RhoA axis across cancers unknown
  11. 2020 High

    Identified PIEZO2 as the bladder and baroreceptor mechanosensor and dissected Gβγ-dependent potentiation, broadening its physiological footprint and sensitization logic.

    Evidence Cell-type-specific conditional KO with cystometry and human genetics; Co-IP and electrophysiology for Nedd4-2; pharmacological PI3K/MAPK dissection with behavior

    PMID:32227462 PMID:32576830 PMID:33057202 PMID:33352230

    Open questions at the time
    • Nedd4-2 regulation shown by single-lab Co-IP/electrophysiology (Medium)
    • Non-cell-autonomous skeletal role mechanism downstream of proprioceptive firing not fully resolved
  12. 2021 High

    Demonstrated PIEZO2 roles in voiding and ultrasonic hearing, showing it cooperates with other channels in non-canonical sensory contexts.

    Evidence Urothelial conditional KO with ATP-release assays; outer-hair-cell KO with audiometry and cochlear Ca2+ imaging

    PMID:34244441 PMID:34464353

    Open questions at the time
    • How PIEZO2 integrates with conventional hair-cell mechanotransduction unresolved
  13. 2022 High

    Resolved polymodal force transmission and lipid/protein tuning, showing distinct mechanical stimuli engage distinct domains and regulators.

    Evidence IDR5 deletion with poking/stretch electrophysiology; TMEM120A and phosphatidic acid lipid regulation; PKA multi-site mutagenesis; coarse-grained MD simulation of lipid enrichment

    PMID:35292651 PMID:35819364 PMID:35861699 PMID:37146970 PMID:39147733

    Open questions at the time
    • Lipid enrichment from MD is computational only, no experimental validation (Low, #43)
    • How PA/TMEM120A regulation operates in vivo across tissues incomplete
  14. 2024 High

    Defined voltage block as a tunable pain gate and identified trafficking and expression regulators, connecting channel availability and biophysics to mechanical pain.

    Evidence R2756 knock-in mice with electrophysiology and behavior; TMC7 and EndoA2/KIF5B Co-IP, conditional KO and rescue; vincristine/actin-tension pharmacology; YTHDF1 m6A regulation of PIEZO2 translation in cardiac fibroblasts

    PMID:37655331 PMID:38475827 PMID:38568807 PMID:38984717 PMID:39498803

    Open questions at the time
    • m6A/YTHDF1 control of PIEZO2 shown in single tissue context (Medium)
    • EndoA2/TMC7 effects validated largely in one lab each
  15. 2025 Medium

    Extended PIEZO2 to metabolic organ crosstalk, showing fat-innervating PIEZO2 neurons shape adipose transcriptional programs.

    Evidence Neuron-specific conditional KO and gain-of-function mutant mice with adipose single-cell transcriptomics

    PMID:40054462

    Open questions at the time
    • Mechanical stimulus sensed in fat not identified
    • Causal signaling from PIEZO2 activation to adipose program not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct force-transmission pathways (membrane tension versus cytoskeleton via IDR5), lipid microenvironment, and the full set of accessory proteins integrate to produce tissue-specific gating thresholds remains unresolved.
  • No unified high-resolution structure of gated/lipid-bound states in corpus
  • In vivo relevance of many regulators tested only heterologously
  • Mechanism converting channel activity to downstream transcriptional/secretory programs incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 5 GO:0005215 transporter activity 3 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-9709957 Sensory Perception 4 R-HSA-112316 Neuronal System 3
Partners
ENDOA2KIF5BMTMR2NEDD4-2PERICENTRINTMC7TMEM120A

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Overexpression of mouse Piezo2 in cells induced rapidly adapting mechanically activated currents; knockdown of Piezo2 in dorsal root ganglion neurons specifically reduced rapidly adapting MA currents. RNA interference knockdown, heterologous overexpression, electrophysiology (patch-clamp) Science High 20813920
2012 Piezo2-mediated mechanically activated currents in sensory neurons are enhanced by bradykinin receptor beta 2 (BDKRB2) activation via PKA and PKC signaling; PKA and PKC agonists directly enhance piezo2 activity, and BDKRB2-mediated effects are abolished by PKA and PKC inhibitors. Heterologous expression, pharmacological activation/inhibition, patch-clamp electrophysiology in sensory neurons and HEK cells Cell reports High 22921401
2013 PIEZO2 gain-of-function mutations (E2727del and I802F) affect channel inactivation kinetics: E2727del slows inactivation and both mutations cause faster recovery from inactivation, resulting in increased channel activity in response to mechanical stimuli, linking PIEZO2 dysfunction to Distal Arthrogryposis Type 5. Electrophysiological characterization of mutant PIEZO2 expressed in cells (patch-clamp), whole-exome sequencing Proceedings of the National Academy of Sciences of the United States of America High 23487782
2013 Epac1 activation potentiates Piezo2-mediated mechanotransduction: the Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents via Piezo2 in a manner dependent on cytosolic calcium and cytoskeleton integrity, but independent of PKC or PKA; in vivo Piezo2 knockdown attenuates 8-pCPT-induced mechanical allodynia. Patch-clamp electrophysiology, pharmacological manipulation, in vivo knockdown, behavioral assays Nature communications High 23575686
2014 Piezo2 is the Merkel-cell mechanotransduction channel: Merkel cells produce touch-sensitive currents in vitro that completely depend on Piezo2, as shown by skin-specific Piezo2 conditional knockout mice lacking Merkel-cell mechanosensitivity; loss also reduces slowly adapting in vivo firing rates and decreases behavioral responses to gentle touch. Conditional knockout mice (skin-specific), patch-clamp electrophysiology, in vivo nerve recordings, behavioral assays Nature High 24717433
2014 Piezo2 is the major transducer for touch sensation: mice lacking Piezo2 in adult sensory neurons and Merkel cells exhibit profound loss of touch sensation; most rapidly adapting MA currents in DRG cultures are absent; mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2 in ex vivo skin-nerve preparations. Conditional knockout mice, patch-clamp electrophysiology in DRG cultures, ex vivo skin-nerve preparation electrophysiology, behavioral assays Nature High 25471886
2014 PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors: CRISPR/Cas9-mediated PIEZO2 gene deletion abolishes mechanosensitivity in hES cell-derived sensory neurons. CRISPR/Cas9 gene deletion, hES/hiPS cell differentiation protocol, patch-clamp electrophysiology Nature neuroscience High 25469543
2014 Combined directed expression of Piezo1 and Piezo2 in chondrocytes produces potentiated mechanically induced Ca2+ signals and electrical currents compared with single-Piezo expression; Piezo1- or Piezo2-specific siRNA inhibits mechanically evoked Ca2+ transients in primary articular chondrocytes. Heterologous co-expression, siRNA knockdown, atomic force microscopy-induced Ca2+ imaging, electrophysiology Proceedings of the National Academy of Sciences of the United States of America Medium 25385580
2015 Piezo2 is the principal mechanotransduction channel for proprioception: Piezo2 is expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs; two independent mouse lines lacking Piezo2 in proprioceptive neurons show severely uncoordinated movements, and stretch-induced firing of proprioceptors in muscle-nerve recordings is markedly reduced. Conditional knockout mice (two independent lines), immunohistochemistry, in vitro patch-clamp, muscle-nerve electrophysiology, behavioral analysis Nature neuroscience High 26551544
2016 Loss-of-function compound mutations in PIEZO2 in humans cause selective loss of discriminative touch perception and profoundly decreased proprioception, confirming PIEZO2 as a determinant of mechanosensation in humans; functional brain imaging and psychophysical testing established the selective sensory deficits. Whole-exome sequencing, in vitro functional assays, messenger RNA assays, functional brain imaging, psychophysical and kinematic testing The New England journal of medicine High 27653382
2016 Piezo2 in mesencephalic trigeminal nucleus proprioceptive neurons produces rapidly adapting mechanically activated currents that are fully dependent on Piezo2; selective deletion of Piezo2 in proprioceptors causes deficits in balance and coordination. Conditional knockout mice (proprioceptor-specific), patch-clamp electrophysiology, behavioral assays Scientific reports Medium 27184818
2016 Mtmr2 (myotubularin related protein-2), a PI phosphatase, was identified as a native Piezo2 interactor in DRG; Mtmr2 attenuates Piezo2-mediated rapidly adapting MA currents through depletion of PI(3,5)P2; a PI(3,5)P2 binding region specific to Piezo2 (not Piezo1) confers sensitivity to Mtmr2 regulation. Mass spectrometry-based native interactomics, co-immunoprecipitation, patch-clamp electrophysiology, pharmacological inhibitors, domain-swapped Piezo2 mutant analysis eLife High 29521261
2016 Pericentrin, identified in a native Piezo2 interactomics screen of mouse DRG, modulates Piezo2 activity and membrane expression in somatosensory neurons. Mass spectrometry-based native interactomics, functional electrophysiology, membrane expression assay Journal of proteome research Medium 27345391
2017 Piezo2 is extensively alternatively spliced, producing isoforms with distinct biophysical properties including differences in ion permeability, sensitivity to calcium modulation, and inactivation kinetics; splicing is cell-type specific even within sensory ganglia. RNA sequencing/isoform profiling, biophysical characterization of splice variants by patch-clamp electrophysiology Cell reports High 29212024
2017 Channel inactivation is the molecular mechanism underlying frequency filtering of Piezo2 (and Piezo1) in response to repetitive mechanical stimuli; human disease-related point mutations that alter inactivation kinetics correspondingly alter frequency filtering. Patch-clamp electrophysiology of heterologously expressed channels, numerical simulations, disease-related point mutations Cell reports High 28636944
2017 D-GsMTx4 (spider peptide) reversibly and dose-dependently inhibits Piezo2 mechanosensitive currents in response to mechanical force, acting on both potency and efficacy. Patch-clamp electrophysiology in HEK293 cells overexpressing human Piezo2, dose-response pharmacology Channels (Austin, Tex.) Medium 28085630
2018 Piezo2 channel-mediated Ca2+ influx activates RhoA in brain metastatic cancer cells, controlling formation and orientation of stress fibers and focal adhesions; mechanism involves Fyn kinase recruitment to the cell leading edge and calpain activation; YAP nuclear translocation and cancer invasion phenotypes depend on this Piezo2-RhoA axis. siRNA knockdown, Ca2+ imaging, RhoA activity assays, confocal microscopy, dominant-positive RhoA rescue experiments, invasion/migration assays Proceedings of the National Academy of Sciences of the United States of America High 29432180
2018 Piezo2 is the primary mechanotransducer in enterochromaffin cells: mechanical stimulation leads to Piezo2-dependent inward ionic currents, intracellular Ca2+ increase, and serotonin release; conditional knockout of intestinal epithelial Piezo2 significantly decreases mechanically stimulated epithelial secretion. Lineage tracing, super-resolution microscopy, patch-clamp electrophysiology, Ca2+ imaging in organoids, ELISA for serotonin, conditional knockout mice, siRNA knockdown Proceedings of the National Academy of Sciences of the United States of America High 30037999
2019 Cold potentiates Piezo2-dependent mechanically activated currents in vertebrate mechanoreceptors; cold sensitivity of Piezo2 is dependent on its blade domains, which render the channel resistant to cold-induced perturbations of the plasma membrane physical properties; this is a distinct mechanism from Piezo1 cold sensitivity. Patch-clamp electrophysiology in mechanoreceptors and heterologous systems with Piezo2 orthologs, domain mutagenesis/swapping Proceedings of the National Academy of Sciences of the United States of America High 31413193
2019 Charged amino acids at the beam domain–CTD interface and hydrophobic interactions between Y2807 of the CTD and pore-lining helices are required for normal mechanosensitivity of PIEZO2; an intrinsically disordered domain adjacent to the beam acts as a cytosolic plug limiting ion permeation by clogging the inner vestibule. Site-directed mutagenesis, patch-clamp electrophysiology (single-channel and whole-cell recordings), structure-guided analysis Proceedings of the National Academy of Sciences of the United States of America High 31235572
2019 Piezo2 is a low-threshold, positive pressure-specific, curvature-sensitive, mechanically activated cation channel; single channel conductance is ~28.6 pS in Merkel cell carcinoma cells; positive pressure ≥5 mmHg activates Piezo2 while negative pressure does not (unlike Piezo1). Patch-clamp electrophysiology (cell-attached and whole-cell), step indentation and pressure application protocols Scientific reports Medium 31015490
2020 PIEZO2 acts as a mechanosensor in both bladder urothelium and innervating sensory neurons; humans and mice lacking functional PIEZO2 have impaired bladder control and deficient bladder-filling sensation; PIEZO2 is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. Conditional knockout mice (urothelial and neuron-specific), cystometry, behavioral bladder assessment, human genetic analysis with patient-reported outcomes Nature High 33057202
2020 Gi-coupled receptor activation potentiates Piezo2 currents via Gβγ in a manner dependent on downstream PI3K and MAPK kinases; sumatriptan (Gi-coupled 5-HT1B/1D receptor agonist) increases mechanical sensitivity in mice, abolished by PI3K and MAPK inhibition; Piezo1 currents are inhibited (not potentiated) by the same pathway. Patch-clamp electrophysiology in DRG neurons and heterologous Piezo2 expression, pharmacological inhibitors, in vivo behavioral assays EMBO reports High 32227462
2020 Nedd4-2 interacts with Piezo2 (co-immunoprecipitation) and inhibits Piezo2 MA currents in co-expressed HEK293T cells; Nedd4-2 upregulation in baroreceptor nodose ganglia neurons of hypertensive rats leads to downregulation of Piezo2, reducing RA-MA currents and impairing baroreflex. Co-immunoprecipitation, patch-clamp electrophysiology in HEK293T cells, siRNA knockdown in vivo, blood pressure measurement, spontaneously hypertensive rat model Pharmacological research Medium 33352230
2021 Urothelial PIEZO2 (expressed in a subset of umbrella cells) is required for normal voiding function; male Piezo2-KO mice exhibit urinary incontinence; dual Piezo1/2-KO mice show decreased urothelial mechanical responses, diminished ATP release, and bladder hypoactivity. Conditional urothelial KO mice (Piezo2, Piezo1, dual), voiding behavior monitoring, urothelial mechanosensitivity assays, ATP release measurement JCI insight High 34464353
2021 PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells: knockout of PIEZO2 in outer hair cells (OHCs) specifically abolishes associative learning during ultrasonic frequency exposure; ultrasonic Ca2+ transduction in cochlea requires both PIEZO2 and the conventional hair-cell mechanotransduction channel. Cell-type-specific knockout mice, audiometry, acoustically associative freezing behavior, ex vivo cochlear Ca2+ imaging Proceedings of the National Academy of Sciences of the United States of America High 34244441
2022 The intrinsically disordered linker IDR5 (between transmembrane helices 12 and 13) is required for activation of PIEZO2 by cytoskeleton-transmitted forces; IDR5 deletion abolishes PIEZO2-mediated inhibition of neurite outgrowth and partially reduces cell indentation sensitivity but does not alter stretch sensitivity, indicating PIEZO2 detects different mechanical stimuli via different force transmission pathways. Site-directed mutagenesis/deletion, patch-clamp electrophysiology (poking and stretch), neurite outgrowth assay Nature communications High 35292651
2022 TMEM120A coexpression decreases the amplitudes of mechanically activated PIEZO2 currents and increases their activation threshold; TMEM120A does not inhibit PIEZO1 or TREK1; siRNA knockdown of Tmem120a in DRG neurons increases rapidly adapting MA current amplitudes and decreases thresholds. Heterologous co-expression, patch-clamp electrophysiology, siRNA knockdown in DRG neurons The Journal of general physiology High 35819364
2022 PKA-dependent modulation of PIEZO2 requires a combination of nine putative PKA phosphorylation sites on four different intracellular disordered regions; mutation of all nine sites abolishes PKA-induced sensitization; PKA modulates PIEZO2 responses to cell indentation but not to pressure-induced membrane stretch, suggesting polymodal mechanosensing through different domains. Phosphorylation site prediction, site-directed mutagenesis, patch-clamp electrophysiology with PKA activation The Journal of biological chemistry High 37146970
2022 Piezo2 in lung microvascular endothelial cells is required for calcium influx and nitric oxide production in response to shear stress; Piezo2 knockdown impairs endothelial alignment, AKT phosphorylation, and NO production, and induces endothelial-to-mesenchymal transition markers. siRNA knockdown in MVECs, Ca2+ imaging, NO production assay, shear stress experiments, Western blotting American journal of physiology. Heart and circulatory physiology Medium 36149769
2022 Loss of UBE3A decreases actin filaments and reduces PIEZO2 expression and function in sensory neurons; linoleic acid supplementation increases PIEZO2 activity and mechano-excitability, and improves gait in Angelman syndrome mice. Ube3a-deficient mouse sensory neurons, human iPSC-derived sensory neurons with UBE3A knockdown, patch-clamp electrophysiology, actin filament staining, dietary intervention with behavioral readout Nature communications Medium 36859399
2023 FM 1-43 dye labeling of somatosensory neurons in vivo is dependent on PIEZO2 activity within peripheral nerve endings; FM 1-43 functions as a functional probe for mechanosensitivity via PIEZO2 activation in vivo. PIEZO2 conditional knockout mice, in vivo FM 1-43 labeling, nerve ending analysis Neuron Medium 37321223
2023 MrgprA3-expressing prurioceptors drive pruritogen-induced alloknesis through Piezo2; histamine and chloroquine sensitize Piezo2 channel function through PLC and PKCδ signaling; genetic ablation of Piezo2 from MrgprA3+ neurons dampens pruritogen-induced alloknesis. Conditional knockout mice (MrgprA3-specific Piezo2 ablation), pharmacological inhibitors (PLC, PKCδ), behavioral assays, patch-clamp electrophysiology Cell reports Medium 36961815
2024 Phosphatidic acid (PA) and lysophosphatidic acid (LPA) selectively inhibit PIEZO2 but not PIEZO1 when applied intracellularly; TMEM120A elevates cellular PA and LPA levels; optogenetic activation of phospholipase D (PLD), which generates PA, inhibits PIEZO2 but not PIEZO1; PLD inhibition increases PIEZO2 activity and mechanical sensitivity in mice. Patch-clamp electrophysiology, lipidomics, optogenetic PLD activation, pharmacological PLD inhibition, in vivo behavioral assays Nature communications High 39147733
2024 PIEZO2 voltage-block regulates mechanical pain sensitivity: mutations at conserved arginine R2756 relieve voltage block and lower mechanical thresholds; in knock-in mice, nociceptor mechanosensitive currents are substantially sensitized while most mechanoreceptor currents are only mildly affected; this leads to behavioral hypersensitivity to noxious mechanical stimuli and ongoing nociceptor activity. Site-directed mutagenesis, knock-in mice (Piezo2R2756H and Piezo2R2756K), patch-clamp electrophysiology in isolated DRG neurons, single-unit extracellular electrophysiology, behavioral assays Brain High 38984717
2024 TMC7 physically interacts with Piezo2 and β-actin in sensory neurons; TMC7 suppresses Piezo2 current amplitudes in co-expressing HEK293 cells; genetic deletion of TMC7 in DRG neurons increases the proportion of rapidly adapting currents and accelerates deactivation kinetics, enhancing mechanosensory sensitivity. Co-immunoprecipitation, patch-clamp electrophysiology in HEK293 cells and DRG neurons, conditional KO mice, behavioral assays Cell reports High 38568807
2024 EndoA2 interacts with Piezo2 (co-immunoprecipitation, proximity ligation) and with KIF5B kinesin, promoting membrane trafficking of Piezo2 in DRG neurons; loss of EndoA2 in NF200+ DRG neurons damages Piezo2-mediated rapidly adapting MA currents, which are rescued by EndoA2 re-expression; KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and mechanical allodynia. Co-immunoprecipitation, proximity ligation assay, patch-clamp electrophysiology, conditional KO mice, behavioral assays in mice and non-human primates Military Medical Research High 38475827
2024 YTHDF1 binds to m6A-modified PIEZO2 mRNA at a specific site (peak_26355) and induces PIEZO2 translation; Piezo2 expression in cardiac fibroblasts drives fibroblast activation and autophagy contributing to cardiac fibrosis; fibroblast-specific Piezo2 deficiency ameliorates cardiac fibrosis. RNA-seq, single-cell sequencing, m6A modification mapping, AAV-mediated fibroblast-specific shRNA knockdown, reconstitution experiments, histological and biochemical assays Cardiovascular research Medium 39498803
2025 PIEZO2 is a major receptor in fat-innervating DRG neurons; PIEZO2 deletion in fat-innervating neurons induces transcriptional programs in adipose tissue resembling sympathetic activation, mirroring DRG ablation; a gain-of-function PIEZO2 mutant shifts adipose phenotypes in the opposite direction. Organ-targeted single-cell RNA sequencing, conditional neuron-specific KO, gain-of-function mutant mice, adipose tissue transcriptomics Cell metabolism Medium 40054462
2024 Vincristine potentiates PIEZO2 rapidly adapting MA currents in DRG neurons by enhancing static plasma membrane tension (SPMT); disruption of actin filaments with cytochalasin D reduces SPMT and abolishes vincristine-induced PIEZO2 potentiation and mechanical hypersensitivity. Patch-clamp electrophysiology in DRG neurons, actin disruption pharmacology, behavioral assays, PIEZO2 gene knockdown Acta pharmaceutica Sinica. B Medium 37655331
2013 GTP-dependent run-up of Piezo2-type rapidly adapting mechanically activated currents occurs in DRG neurons and in HEK293 cells heterologously expressing Piezo2; the run-up requires GTP (not GDP) in the intracellular solution and is absent in perforated patch configuration, indicating GTP-dependent intracellular regulation of Piezo2 channel function. Whole-cell patch-clamp electrophysiology in DRG neurons and HEK293 cells, perforated patch configuration, nucleotide substitution Molecular brain Medium 24344923
2016 Piezo2 expressed in the enterochromaffin (EC) cell model leads to mechanosensitive inward non-selective cation currents; both currents and serotonin release are inhibited by Piezo2 siRNA and antagonists (Gd3+ and D-GsMTx4); mucosal pressure increases serotonin release via submucosal 5-HT3 and 5-HT4 receptors. siRNA knockdown, patch-clamp electrophysiology, ELISA for serotonin, pharmacological inhibitors, Ussing chamber secretion assay The Journal of physiology Medium 27392819
2020 Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity: loss of Piezo2 in proprioceptive neurons (but not in chondrogenic or osteogenic lineages) leads to spine malalignment and hip dysplasia in mice, demonstrating a non-cell-autonomous role of proprioceptive PIEZO2 in joint morphogenesis. Lineage-specific conditional KO mice (proprioceptive, chondrogenic, osteogenic lineages), MRI/microCT skeletal analysis, genetic epistasis with Runx3 and Egr3 knockouts Nature communications High 32576830
2022 Molecular dynamics simulations reveal that Piezo2 alters its local membrane composition, becoming enriched with specific lipids including phosphoinositides, and forms specific long-term interactions with various lipids at functionally relevant sites; this provides a structural basis for lipid-mediated regulation. Coarse-grained molecular dynamics simulations in complex mammalian membrane The Journal of general physiology Low 35861699

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science (New York, N.Y.) 2442 20813920
2014 Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 687 25471886
2014 Piezo2 is required for Merkel-cell mechanotransduction. Nature 595 24717433
2015 Piezo2 is the principal mechanotransduction channel for proprioception. Nature neuroscience 463 26551544
2014 Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proceedings of the National Academy of Sciences of the United States of America 391 25385580
2016 The Role of PIEZO2 in Human Mechanosensation. The New England journal of medicine 331 27653382
2018 A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release. Proceedings of the National Academy of Sciences of the United States of America 225 30037999
2013 Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. Proceedings of the National Academy of Sciences of the United States of America 191 23487782
2013 A role for Piezo2 in EPAC1-dependent mechanical allodynia. Nature communications 188 23575686
2018 Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses. Proceedings of the National Academy of Sciences of the United States of America 183 29432180
2020 PIEZO2 in sensory neurons and urothelial cells coordinates urination. Nature 182 33057202
2014 Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. American journal of human genetics 175 24726473
2012 Inflammatory signals enhance piezo2-mediated mechanosensitive currents. Cell reports 166 22921401
2018 Piezo2 channel-Merkel cell signaling modulates the conversion of touch to itch. Science (New York, N.Y.) 157 29724954
2016 Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces. The Journal of physiology 144 27392819
2017 Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction. Current topics in membranes 108 28728825
2017 Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction. Cell reports 107 29212024
2017 Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels. Cell reports 103 28636944
2014 PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors. Nature neuroscience 99 25469543
2023 Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis. Nature communications 93 37120427
2016 A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons. Scientific reports 93 27184818
2017 An Ultrasensitive, Visco-Poroelastic Artificial Mechanotransducer Skin Inspired by Piezo2 Protein in Mammalian Merkel Cells. Advanced materials (Deerfield Beach, Fla.) 77 28185323
2020 Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity. Nature communications 74 32576830
2020 Piezo2 Mediates Low-Threshold Mechanically Evoked Pain in the Cornea. The Journal of neuroscience : the official journal of the Society for Neuroscience 71 33055278
2021 Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception. JCI insight 70 34464353
2014 Piezo2 expression in corneal afferent neurons. The Journal of comparative neurology 69 24549492
2021 Piezo2 mechanosensitive ion channel is located to sensory neurons and nonneuronal cells in rat peripheral sensory pathway: implications in pain. Pain 66 34285153
2017 Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4. Channels (Austin, Tex.) 64 28085630
2016 Biallelic Loss of Proprioception-Related PIEZO2 Causes Muscular Atrophy with Perinatal Respiratory Distress, Arthrogryposis, and Scoliosis. American journal of human genetics 61 27843126
2016 Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects. Journal of human genetics 59 27974811
2016 Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures. Clinical genetics 58 27607563
2019 Structure-guided examination of the mechanogating mechanism of PIEZO2. Proceedings of the National Academy of Sciences of the United States of America 56 31235572
2022 Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2. Nature communications 55 35292651
2016 Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability. Oncotarget 55 27329839
2019 Repeated Low-Level Blast Overpressure Leads to Endovascular Disruption and Alterations in TDP-43 and Piezo2 in a Rat Model of Blast TBI. Frontiers in neurology 51 31417481
2019 The Piezo2 ion channel is mechanically activated by low-threshold positive pressure. Scientific reports 50 31015490
2018 The increased expression of Piezo1 and Piezo2 ion channels in human and mouse bladder carcinoma. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 49 30010255
2023 Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome. Nature communications 48 36859399
2019 Piezo2 integrates mechanical and thermal cues in vertebrate mechanoreceptors. Proceedings of the National Academy of Sciences of the United States of America 48 31413193
2014 Piezo2 channel conductance and localization domains in Merkel cells of rat whisker hair follicles. Neuroscience letters 43 24911969
2018 Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons. eLife 42 29521261
2017 Merkel cells and Meissner's corpuscles in human digital skin display Piezo2 immunoreactivity. Journal of anatomy 42 28905996
2017 Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome? Journal of neurogastroenterology and motility 39 28044050
2017 Piezo2 Expression in Mechanosensitive Dental Primary Afferent Neurons. Journal of dental research 39 28388364
2021 The effect of IL-6/Piezo2 on the trigeminal neuropathic pain. Aging 38 33893246
2021 Piezo2-peripheral baroreceptor channel expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses. Journal of integrative neuroscience 37 34997707
2015 A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation. American journal of medical genetics. Part A 36 25712306
2015 Contribution of Piezo2 to endothelium-dependent pain. Molecular pain 36 26497944
2023 Labeling PIEZO2 activity in the peripheral nervous system. Neuron 35 37321223
2021 PIEZO2 mediates ultrasonic hearing via cochlear outer hair cells in mice. Proceedings of the National Academy of Sciences of the United States of America 35 34244441
2022 Loss of lung microvascular endothelial Piezo2 expression impairs NO synthesis, induces EndMT, and is associated with pulmonary hypertension. American journal of physiology. Heart and circulatory physiology 30 36149769
2022 TMEM120A/TACAN inhibits mechanically activated PIEZO2 channels. The Journal of general physiology 29 35819364
2022 Mechano-Sensing Channel PIEZO2 Enhances Invasive Phenotype in Triple-Negative Breast Cancer. International journal of molecular sciences 29 36077309
2021 Piezo2 Knockdown Inhibits Noxious Mechanical Stimulation and NGF-Induced Sensitization in A-Delta Bone Afferent Neurons. Frontiers in physiology 29 34335288
2016 Familial Gordon syndrome associated with a PIEZO2 mutation. American journal of medical genetics. Part A 29 27714920
2020 Gi-coupled receptor activation potentiates Piezo2 currents via Gβγ. EMBO reports 28 32227462
2024 Piezo2 voltage-block regulates mechanical pain sensitivity. Brain : a journal of neurology 27 38984717
2022 Piezo2 expression and its alteration by mechanical forces in mouse mesangial cells and renin-producing cells. Scientific reports 27 35273307
2022 Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy. Journal of molecular neuroscience : MN 26 35507012
2016 The potential role of Piezo2 in the mediation of visceral sensation. Neuroscience letters 26 27481627
2022 Mechanosensitive Piezo1 and Piezo2 ion channels in craniofacial development and dentistry: Recent advances and prospects. Frontiers in physiology 24 36338498
2021 Extracellular ATP and cAMP signaling promote Piezo2-dependent mechanical allodynia after trigeminal nerve compression injury. Journal of neurochemistry 24 34757653
2019 A Cross-Species Analysis Reveals a General Role for Piezo2 in Mechanosensory Specialization of Trigeminal Ganglia from Tactile Specialist Birds. Cell reports 24 30784581
2016 Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons. Journal of proteome research 24 27345391
2015 The biophysics of piezo1 and piezo2 mechanosensitive channels. Biophysical chemistry 23 26259784
2017 PIEZO2 as the anomalous mechanotransducer channel in auditory hair cells. The Journal of physiology 22 28983916
2013 GTP-dependent run-up of Piezo2-type mechanically activated currents in rat dorsal root ganglion neurons. Molecular brain 22 24344923
2020 Piezo2 channel in nodose ganglia neurons is essential in controlling hypertension in a pathway regulated directly by Nedd4-2. Pharmacological research 21 33352230
2022 Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1-Piezo2 Axis. Frontiers in endocrinology 20 35865309
2024 Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity. Nature communications 19 39147733
2024 Epitranscriptomic regulation of cardiac fibrosis via YTHDF1-dependent PIEZO2 mRNA m6A modification. Cardiovascular research 18 39498803
2023 MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel. Cell reports 18 36961815
2023 Miswired Proprioception in Amyotrophic Lateral Sclerosis in Relation to Pain Sensation (and in Delayed Onset Muscle Soreness)-Is Piezo2 Channelopathy a Principal Transcription Activator in Proprioceptive Terminals Besides Being the Potential Primary Damage? Life (Basel, Switzerland) 18 36983813
2022 PIEZO2 ion channels in proprioception. Current opinion in neurobiology 18 35689908
2025 Deficiency of Endothelial Piezo2 Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension. Hypertension (Dallas, Tex. : 1979) 17 39758000
2024 TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction. Cell reports 17 38568807
2023 Upregulation of Piezo2 in the mesangial, renin, and perivascular mesenchymal cells of the kidney of Dahl salt-sensitive hypertensive rats and its reversal by esaxerenone. Hypertension research : official journal of the Japanese Society of Hypertension 17 36810623
2022 The acquisition of mechanoreceptive competence by human digital Merkel cells and sensory corpuscles during development: An immunohistochemical study of PIEZO2. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 17 35523396
2020 Maturational Changes in Mouse Cutaneous Touch and Piezo2-Mediated Mechanotransduction. Cell reports 17 32697985
2020 Glans clitoris innervation: PIEZO2 and sexual mechanosensitivity. Journal of anatomy 17 32996126
2024 Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking. Military Medical Research 16 38475827
2024 Piezo1 and Piezo2 collectively regulate jawbone development. Development (Cambridge, England) 16 38619396
2022 Expression of Piezo2 in the Dental Pulp, Sensory Root, and Trigeminal Ganglion and Its Coexpression with Vesicular Glutamate Transporters. Journal of endodontics 16 35952898
2021 Dorsal root ganglia NR2B-mediated Epac1-Piezo2 signaling pathway contributes to mechanical allodynia of bone cancer pain. Oncology letters 16 33692870
2022 Characterizing the lipid fingerprint of the mechanosensitive channel Piezo2. The Journal of general physiology 15 35861699
2019 PIEZO2 deficiency is a recognizable arthrogryposis syndrome: A new case and literature review. American journal of medical genetics. Part A 15 30941898
2025 A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation. Cell metabolism 14 40054462
2023 PKA mediates modality-specific modulation of the mechanically gated ion channel PIEZO2. The Journal of biological chemistry 14 37146970
2018 Novel mutations in TPM2 and PIEZO2 are responsible for distal arthrogryposis (DA) 2B and mild DA in two Chinese families. BMC medical genetics 14 30285720
2025 Piezo2 Is a Key Mechanoreceptor in Lung Fibrosis that Drives Myofibroblast Differentiation. The American journal of pathology 13 39855300
2024 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.) 13 38754025
2023 PIEZO2 promotes cell proliferation and metastasis in colon carcinoma through the SLIT2/ROBO1/VEGFC pathway. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 13 36753373
2024 Piezo2 Contributes to Traumatic Brain Injury by Activating the RhoA/ROCK1 Pathways. Molecular neurobiology 12 38388773
2024 Mechanosensitive Ion Channels Piezo1 and Piezo2 Mediate Motor Responses In Vivo During Transcranial Focused Ultrasound Stimulation of the Rodent Cerebral Motor Cortex. IEEE transactions on bio-medical engineering 12 38748529
2023 Potentiation of PIEZO2 mechanically-activated currents in sensory neurons mediates vincristine-induced mechanical hypersensitivity. Acta pharmaceutica Sinica. B 12 37655331
2023 Differential expression of PIEZO1 and PIEZO2 mechanosensitive channels in ocular tissues implicates diverse functional roles. Experimental eye research 12 37820892
2023 Immunolocalization of the mechanogated ion channels PIEZO1 and PIEZO2 in human and mouse dental pulp and periodontal ligament. Anatomical record (Hoboken, N.J. : 2007) 12 37975162
2022 A pan-cancer analysis reveals the genetic alterations and immunotherapy of Piezo2 in human cancer. Frontiers in genetics 12 35991548
2024 Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance. The Journal of experimental medicine 11 39167075
2021 Piezo2 downregulation via the Cre-lox system affects aqueous humor dynamics in mice. Molecular vision 11 34220183

Missed literature

Know a paper Affinage missed for PIEZO2? Flag it for the maintainers and the community.

No submissions yet.