ArticleJournal of cellular physiology2015
Phospholipase C epsilon (PLCε) induced TRPC6 activation: a common but redundant mechanism in primary podocytes.
Article in Journal of cellular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Mechanisms of podocyte injury in genetic kidney disease.Pediatric nephrology (Berlin, Germany) · 2025Review
- α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6.Advances in experimental medicine and biology · 2023Article
- The normalized slope conductance as a tool for quantitative analysis of current-voltage relations.Biophysical journal · 2022Article
- GαFrontiers in cell and developmental biology · 2022Review
- Bioinformatics analysis reveals the roles of cytoskeleton protein transgelin in occurrence and development of proteinuria.Translational pediatrics · 2021Article
- TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema.JCI insight · 2020Article
- Hypertension induces glomerulosclerosis in phospholipase C-ε1 deficiency.American journal of physiology. Renal physiology · 2020Article
- Store-operated CaScientific reports · 2020Article
- PLCε1 suppresses tumor growth by regulating murine T cell mobilization.Clinical and experimental immunology · 2020Article
- TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.Pflugers Archiv : European journal of physiology · 2018Article
- Pharmacological inhibition of focal segmental glomerulosclerosis-related, gain of function mutants of TRPC6 channels by semi-synthetic derivatives of larixol.British journal of pharmacology · 2017Article
- Role of phosphatase and tensin homolog in hypoxic pulmonary vasoconstriction.Cardiovascular research · 2017Article
- PLCε1 regulates SDF-1α-induced lymphocyte adhesion and migration to sites of inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- PLCE1 Promotes Esophageal Cancer Cell Progression by Maintaining the Transcriptional Activity of Snail.Neoplasia (New York, N.Y.) · 2017Article
- Targeting the podocyte cytoskeleton: from pathogenesis to therapy in proteinuric kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016Review
- Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization.Journal of the American Society of Nephrology : JASN · 2016Article
- 20-Hydroxyeicosatetraenoic Acid (20-HETE) Modulates Canonical Transient Receptor Potential-6 (TRPC6) Channels in Podocytes.Frontiers in physiology · 2016Article
- Cholesterol-Dependent Gating Effects on Ion Channels.Advances in experimental medicine and biologyReview
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
In eukaryotic cells, activation of phospholipase C (PLC)-coupled membrane receptors by hormones leads to an increase in the intracellular Ca(2+) concentration [Ca(2+) ]i . Catalytic activity of PLCs results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) which opens DAG-sensitive classical transient receptor channels 3, 6, and 7 (TRPC3/6/7), initiating Ca(2+) influx from the extracellular space. Patients with focal segmental glomerulosclerosis (FSGS) express gain-of-function mutants of TRPC6, while others carry loss-of-function mutants of PLCε, raising the intriguing possibility that both proteins interact and might work in the same signalling pathway. While TRPC6 activation by PLCβ and PLCγ isozymes was extensively studied, the role of PLCε in TRPC6 activation remains elusive. TRPC6 was co-immunoprecipitated with PLCε in a heterologous overexpression system in HEK293 cells as well as in freshly isolated murine podocytes. Receptor-operated TRPC6 currents in HEK293 cells expressing TRPC6 were reduced by a specific PLCε siRNA and by a PLCε loss-of-function mutant isolated from a patient with FSGS. PLCε-induced TRPC6 activation was also identified in murine embryonic fibroblasts (MEFs) lacking Gαq/11 proteins. Further analysis of the signal transduction pathway revealed a Gα12/13 Rho-GEF activation which induced Rho-mediated PLCε stimulation. Therefore, we identified a new pathway for TRPC6 activation by PLCε. PLCε-/- podocytes however, were undistinguishable from WT podocytes in their angiotensin II-induced formation of actin stress fibers and their GTPγS-induced TRPC6 activation, pointing to a redundant role of PLCε-mediated TRPC6 activation at least in podocytes.
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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.