ArticleNature communications2023
TRPV4-Rho GTPase complex structures reveal mechanisms of gating and disease.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- An update on regulation of the polymodal TRPV4 channel by protein phosphorylation.Channels (Austin, Tex.) · 2026Review
- Mechanobiological Response of Osteocyte TRPV4 Base on the Piezoelectricity of Bone Matrix.Annals of biomedical engineering · 2026Article
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Thermodynamic coupling between cold and heat activations of TRPV2.Scientific reports · 2026Article
- Ciliary IFT88 inhibits intervertebral disc degeneration under excessive mechanical stress by regulating endplate cartilage calcification.Journal of advanced research · 2026Article
- Microglial Lyn Kinase-TRPV4 axis mediates social deficits in a maternal immune activation model.Journal of neuroinflammation · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Temperature-induced structural changes in thermosensitive transient receptor potential channels (thermoTRPs).Frontiers in molecular neuroscience · 2026Review
- Visualizing insecticide control of insect TRP channel function and assembly.Nature communications · 2025Article
- Pathway-dependent cold activation of heat-responsive TRPV channels.Scientific reports · 2025Article
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Structural and mechanistic insights into symmetry conversion in plant GORK K+ channel regulation.Protein & cell · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Article
- Hypotonic stimuli promote osteocyte dendrite formation by modulating actin dynamics via the TRPV4-CDC42 signaling pathway.Materials today. Bio · 2025Article
- Blocking axon-glial mechanotransduction to prevent concussive brain injury.Acta neuropathologica communications · 2025Article
- PIP2 regulation of TRPV4 channels: Binding sites and dynamic coupling.Biophysical journal · 2025Article
- TRPV4 controls circadian and pathological ocular hypertension.The Journal of physiology · 2025Article
- Structural insights into TRPV2 modulation by probenecid.Nature structural & molecular biology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Crosstalk between ion channels and small GTPases is critical during homeostasis and disease, but little is known about the structural underpinnings of these interactions. TRPV4 is a polymodal, calcium-permeable cation channel that has emerged as a potential therapeutic target in multiple conditions. Gain-of-function mutations also cause hereditary neuromuscular disease. Here, we present cryo-EM structures of human TRPV4 in complex with RhoA in the ligand-free, antagonist-bound closed, and agonist-bound open states. These structures reveal the mechanism of ligand-dependent TRPV4 gating. Channel activation is associated with rigid-body rotation of the intracellular ankyrin repeat domain, but state-dependent interaction with membrane-anchored RhoA constrains this movement. Notably, many residues at the TRPV4-RhoA interface are mutated in disease and perturbing this interface by introducing mutations into either TRPV4 or RhoA increases TRPV4 channel activity. Together, these results suggest that RhoA serves as an auxiliary subunit for TRPV4, regulating TRPV4-mediated calcium homeostasis and disruption of TRPV4-RhoA interactions can lead to TRPV4-related neuromuscular disease. These insights will help facilitate TRPV4 therapeutics development.
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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 OpenQuestion graph.