ArticleMolecular biology of the cell2011
Tyrosine phosphorylation-dependent activation of TRPC6 regulated by PLC-γ1 and nephrin: effect of mutations associated with focal segmental glomerulosclerosis.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 74 citations in OpenAlex.
- Lipid Regulation of Mechanosensitive Ion Channels.International journal of molecular sciences · 2026Review
- A novel TRPC6 variant (c.131C>T, p.(Pro44Leu)) associated with focal segmental glomerulosclerosis: a case report.Frontiers in genetics · 2026Article
- Revisiting nephrin signaling and its specialized effects on the uniquely adaptable podocyte.The Biochemical journal · 2025Review
- Effective calcineurin inhibitor treatment in adult-onset steroid-resistant nephrotic syndrome with a novel splice donor site variant of TRPC6: a case report.CEN case reports · 2025Article
- Genotype-Phenotype Correlations with TRPC6-Associated Podocytopathy.Journal of the American Society of Nephrology : JASN · 2025Article
- Article
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation.iScience · 2023Article
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Increase in membrane surface expression and phosphorylation of TRPC3 related to olfactory dysfunction in α-synuclein transgenic mice.Journal of cellular and molecular medicine · 2022Article
- Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade.BMC complementary medicine and therapies · 2021Article
- Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins.PloS one · 2021Article
- New insight into podocyte slit diaphragm, a therapeutic target of proteinuria.Clinical and experimental nephrology · 2020Review
- Review
- Research Progress in Acute Hypertensive Renal Injury by "Journal of translational internal medicine · 2019Review
- TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, and Motility.Journal of the American Society of Nephrology : JASN · 2019Article
- Contribution of Coiled-Coil Assembly to CaJournal of the American Society of Nephrology : JASN · 2019Article
- Transmembrane insertases andThe Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transient receptor potential canonicals (TRPCs) play important roles in the regulation of intracellular calcium concentration. Mutations in the TRPC6 gene are found in patients with focal segmental glomerulosclerosis (FSGS), a proteinuric disease characterized by dysregulated function of renal glomerular epithelial cells (podocytes). There is as yet no clear picture for the activation mechanism of TRPC6 at the molecular basis, however, and the association between its channel activity and pathogenesis remains unclear. We demonstrate here that tyrosine phosphorylation of TRPC6 induces a complex formation with phospholipase C (PLC)-γ1, which is prerequisite for TRPC6 surface expression. Furthermore, nephrin, an adhesion protein between the foot processes of podocytes, binds to phosphorylated TRPC6 via its cytoplasmic domain, competitively inhibiting TRPC6-PLC-γ1 complex formation, TRPC6 surface localization, and TRPC6 activation. Importantly, FSGS-associated mutations render the mutated TRPC6s insensitive to nephrin suppression, thereby promoting their surface expression and channel activation. These results delineate the mechanism of TRPC6 activation regulated by tyrosine phosphorylation, and imply the cell type-specific regulation, which correlates the FSGS mutations with deregulated TRPC6 channel activity.
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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.