ArticleProceedings of the National Academy of Sciences of the United States of America2016
Membrane translocation of TRPC6 channels and endothelial migration are regulated by calmodulin and PI3 kinase activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 52 citations in OpenAlex.
- TRPC6-Mediated CaCells · 2026Article
- The CaPediatric nephrology (Berlin, Germany) · 2025Review
- β-Arrestin pathway activation by selective ATR1 agonism promotes calcium influx in podocytes, leading to glomerular damage.Clinical science (London, England : 1979) · 2023Article
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Tree of life: endothelial cell in norm and disease, the good guy is a partner in crime!Anatomy & cell biology · 2023Review
- p38 MAPK activation and STIM1-Orai3 association mediate TRPC6 externalization.American journal of physiology. Cell physiology · 2023Article
- iPLA2 inhibition blocks LysoPC-induced TRPC6 externalization and promotes Re-endothelialization of carotid injuries in hypercholesterolemic mice.Cell calcium · 2023Article
- p85α regulatory subunit isoform controls PI3-kinase and TRPC6 membrane translocation.Cell calcium · 2023Article
- Finnish-specific AKT2 gene variant leads to impaired insulin signalling in myotubes.Journal of molecular endocrinology · 2023Article
- α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6.Advances in experimental medicine and biology · 2023Article
- How filopodia respond to calcium in the absence of a calcium-binding structural protein: non-channel functions of TRP.Cell communication and signaling : CCS · 2022Article
- The TRPC1 Channel Forms a PI3K/CaM Complex and Regulates Pancreatic Ductal Adenocarcinoma Cell Proliferation in a CaInternational journal of molecular sciences · 2022Article
- TRPC1 promotes the genesis and progression of colorectal cancer via activating CaM-mediated PI3K/AKT signaling axis.Oncogenesis · 2021Article
- Mechanosensitive ion channels in cell migration.Cells & development · 2021Review
- Inhibition of P110α and P110δ catalytic subunits of PI3 kinase reverses impaired arterial healing after injury in hypercholesterolemic male mice.American journal of physiology. Cell physiology · 2021Article
- P110α and P110δ catalytic subunits of PI3 kinase regulate lysophosphatidylcholine-induced TRPC6 externalization.American journal of physiology. Cell physiology · 2021Article
- Perfusion reduces bispecific antibody aggregation via mitigating mitochondrial dysfunction-induced glutathione oxidation and ER stress in CHO cells.Scientific reports · 2020Article
- Review
- The Role of Calmodulin in Tumor Cell Migration, Invasiveness, and Metastasis.International journal of molecular sciences · 2020Review
- Canonical transient receptor potential 6 channel deficiency promotes smooth muscle cells dedifferentiation and increased proliferation after arterial injury.JVS-vascular science · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels leading to inhibition of endothelial cell (EC) migration in vitro and delayed EC healing of arterial injuries in vivo. The precise mechanism through which lysoPC activates TRPC6 channels is not known, but calmodulin (CaM) contributes to the regulation of TRPC channels. Using site-directed mutagenesis, cDNAs were generated in which Tyr(99) or Tyr(138) of CaM was replaced with Phe, generating mutant CaM, Phe(99)-CaM, or Phe(138)-CaM, respectively. In ECs transiently transfected with pcDNA3.1-myc-His-Phe(99)-CaM, but not in ECs transfected with pcDNA3.1-myc-His-Phe(138)-CaM, the lysoPC-induced TRPC6-CaM dissociation and TRPC6 externalization was disrupted. Also, the lysoPC-induced increase in intracellular calcium concentration was inhibited in ECs transiently transfected with pcDNA3.1-myc-His-Phe(99)-CaM. Blocking phosphorylation of CaM at Tyr(99) also reduced CaM association with the p85 subunit and subsequent activation of phosphatidylinositol 3-kinase (PI3K). This prevented the increase in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the translocation of TRPC6 to the cell membrane and reduced the inhibition of EC migration by lysoPC. These findings suggest that lysoPC induces CaM phosphorylation at Tyr(99) by a Src family kinase and that phosphorylated CaM activates PI3K to produce PIP3, which promotes TRPC6 translocation to the cell membrane.
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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.