ArticleAmerican journal of physiology. Cell physiology2013
Opposing effects of podocin on the gating of podocyte TRPC6 channels evoked by membrane stretch or diacylglycerol.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 113 citations in OpenAlex.
- Mechanobiological landscape of muscle stem cells.Skeletal muscle · 2026Review
- Podocin oligomers regulate the ordering of nephrin chains, providing the molecular basis ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Structural and functional insights of the podocyte slit diaphragm complex.Tissue barriers · 2026Review
- Preclinical approaches to studying liver and kidney fibrosis: models and methodologies.Frontiers in pharmacology · 2026Review
- In situ structure of a gap junction-stomatin complex.Science advances · 2025Article
- TRPC6 effects on albumin permeation, nephrin shedding, and apoptosis in podocytes: Role of calcineurin and metalloproteases.Physiological reports · 2025Article
- Elevated hydrostatic pressure destabilizes VE-cadherin junctions in a time and shear stress dependent manner: An endothelium-on-chip study.APL bioengineering · 2025Article
- Revisiting nephrin signaling and its specialized effects on the uniquely adaptable podocyte.The Biochemical journal · 2025Review
- Mechanisms of podocyte injury in genetic kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- Article
- TRPC6 is a mechanosensitive channel essential for ultrasound neuromodulation in the mammalian brain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Transplantation of decellularized porcine kidney grafts repopulated with primary human cells demonstrates filtration function in pigs.Communications medicine · 2024Article
- The roles of TRPC6 in renal tubular disorders: a narrative review.Renal failure · 2024Review
- Non-voltage-gated CaAmerican journal of physiology. Renal physiology · 2024Review
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- Role of biophysics and mechanobiology in podocyte physiology.Nature reviews. Nephrology · 2024Review
- Vulnerability of Store-Operated Calcium Entry to Inhibitors and Microenvironment in Cells of Different Breast Cancer Subtypes.Life (Basel, Switzerland) · 2024Article
- Mechanosensitive Cation Channel Piezo1 Is Involved in Renal Fibrosis Induction.International journal of molecular sciences · 2024Review
- Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1.Arthritis research & therapy · 2023Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Gain-of-function mutations in the transient receptor potential (TRP) cation channel subfamily C member 6 (TRPC6) gene and mutations in the NPHS2 gene encoding podocin result in nephrotic syndromes. The purpose of this study was to determine the functional significance of biochemical interactions between these proteins. We observed that gating of TRPC6 channels in podocytes is markedly mechanosensitive and can be activated by hyposmotic stretch or indentation of the plasma membrane. Stretch activation of cationic currents was blocked by small interfering RNA knockdown of TRPC6, as well as by SKF-96365 or micromolar La(3+). Stretch activation of podocyte TRPC6 persisted in the presence of inhibitors of phospholipase C (U-73122) and phospholipase A2 (ONO-RS-082). Robust stretch responses also persisted when recording electrodes contained guanosine 5'-O-(2-thiodiphosphate) at concentrations that completely suppressed responses to ANG II. Stretch responses were enhanced by cytochalasin D but were abolished by the peptide GsMTx4, suggesting that forces are transmitted to the channels through the plasma membrane. Podocin and TRPC6 interact at their respective COOH termini. Knockdown of podocin markedly increased stretch-evoked activation of TRPC6 but nearly abolished TRPC6 activation evoked by a diacylglycerol analog. These data suggest that podocin acts as a switch to determine the preferred mode of TRPC6 activation. They also suggest that podocin deficiencies will result in Ca(2+) overload in foot processes, as with gain-of-function mutations in the TRPC6 gene. Finally, they suggest that mechanical activation of TRP family channels and the preferred mode of TRP channel activation may depend on whether members of the stomatin/prohibitin family of hairpin loop proteins are present.
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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.