ArticleThe Journal of clinical investigation2024
Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Piezo-type mechanosensitive ion channel component 1: a mechano-bioenergetic transducer in the tumour microenvironment.Annals of medicine · 2026Review
- 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
- ERS Congress 2025: highlights from the Basic and Translational Sciences Assembly.ERJ open research · 2026Article
- From Mechanical Cues to Lung Injury: Mapping the Global Landscape and Frontiers of Mechanoregulation Through Bibliometrics and LDA Analysis.Journal of cellular and molecular 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
- Piezo channels in tumors.Journal of cancer research and clinical oncology · 2026Review
- Adenosine-Specific Transcriptional Programs in Murine Connective Tissue-Type Mast Cells.ACS pharmacology & translational science · 2026Article
- Spatial proteomics for the analysis of host-pathogen interactions in mice lungs infected withmicroLife · 2026Article
- 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
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 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
- Mechanotransduction: A Master Regulator of Alveolar Cell Fate Determination.Bioengineering (Basel, Switzerland) · 2025Review
- Osmosensor TMEM63B facilitates insulin secretion in pancreatic β-cells.Science China. Life sciences · 2025Article
- Cation Channel TMEM63A Autonomously Facilitates Oligodendrocyte Differentiation at an Early Stage.Neuroscience bulletin · 2025Article
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.
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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.