ArticleNeuron2023
TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels.
Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 80 citations in OpenAlex.
- Lipid flip-flop in biological membranes: through the lens of TMEM16F.Physiological reviews · 2026Review
- A TMEM63B variant with enhanced mechanosensitive channel activity and acquired lipid scramblase function.The Journal of general physiology · 2026Article
- Loss of novel mechanosensitive ion channel TMEM63A impairs osteogenic differentiation and proliferation via disruption of cellular mechanotransduction.Mechanobiology in medicine · 2026Article
- Bi-allelic loss-of-function variants in TMEM63B cause syndromic surfactant dysfunction disorder.American journal of human genetics · 2026Article
- TMEM63B regulates nucleocytoplasmic transport and placental development.Nature communications · 2026Article
- Functional Divergence and Emerging Roles of the ANO-TMC-TMEM63 Channel Families in Olfaction and Gustation.International journal of molecular sciences · 2026Review
- TMEM63 proteins act as mechanically activated cholesterol modulated lipid scramblases contributing to membrane mechano-resilience.Nature communications · 2026Article
- Mechanosensitive TMEM63 Ion Channels: Structure, Gating Mechanism, and Emerging Physiological and Pathological Roles.Results and problems in cell differentiation · 2026Review
- From plasma membrane to lysosomes: expanding roles of TMEM63/OSCA channels in mechanosensation and intracellular signaling.Frontiers in pharmacology · 2026Review
- Targeting Tmem63b and Piezo2 in C-fiber low-threshold mechanoreceptors: Limitation of Vglut3-IRES-Cre.Biophysical journal · 2025Article
- Glial Ion Channels in Myelin Pathophysiology: Insights from Leukodystrophies.Life (Basel, Switzerland) · 2025Review
- Blood plasma proteomics for detecting potential biomarkers for tick resistance in a tropically adapted beef cattle breed.BMC genomics · 2025Article
- Transmembrane protein TMEM98 as a multifunctional regulator in cancer: from signaling pathways to translational implications.Journal of translational medicine · 2025Review
- Article
- Lysosomal ion channels and pain.Pain reports · 2025Review
- TMEM63A, associated with hypomyelinating leukodystrophies, is an evolutionarily conserved regulator of myelination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unnatural Amino Acid Photo-Crosslinking Sheds Light on Gating of the Mechanosensitive Ion Channel OSCA1.2.International journal of molecular sciences · 2025Article
- Groove architecture controls lipid scrambling in simulations of protein and model systems.bioRxiv : the preprint server for biology · 2025Article
- Osmosensor TMEM63B facilitates insulin secretion in pancreatic β-cells.Science China. Life sciences · 2025Article
- Genetic Insights into Brain Morphology: a Genome-Wide Association Study of Cortical Thickness and TNeuroinformatics · 2025Article
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12 authors at 5 institutions in 2 countries.
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Abstract
OSCA/TMEM63s form mechanically activated (MA) ion channels in plants and animals, respectively. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. Here, we uncover an unanticipated monomeric configuration of TMEM63 proteins. Structures of TMEM63A and TMEM63B (referred to as TMEM63s) revealed a single highly restricted pore. Functional analyses demonstrated that TMEM63s are bona fide mechanosensitive ion channels, characterized by small conductance and high thresholds. TMEM63s possess evolutionary variations in the intracellular linker IL2, which mediates dimerization in OSCAs. Replacement of OSCA1.2 IL2 with TMEM63A IL2 or mutations to key variable residues resulted in monomeric OSCA1.2 and MA currents with significantly higher thresholds. Structural analyses revealed substantial conformational differences in the mechano-sensing domain IL2 and gating helix TM6 between TMEM63s and OSCA1.2. Our studies reveal that mechanosensitivity in OSCA/TMEM63 channels is affected by oligomerization and suggest gating mechanisms that may be shared by OSCA/TMEM63, TMEM16, and TMC channels.
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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.