ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5) P₂.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 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, 53 citations in OpenAlex.
- Drafting the calmodulation playbook: Emerging structural insights into transient receptor potential channel regulation by calmodulin.The Journal of physiology · 2026Review
- The locking mechanism of human TRPV6 inhibition by intracellular magnesium.Nature communications · 2025Article
- PIP2 regulation of TRPV4 channels: Binding sites and dynamic coupling.Biophysical journal · 2025Article
- A novel TRPV5/6-like channel from a scleractinian coral.PloS one · 2025Article
- Molecular pharmacology of the onco-TRP channel TRPV6.Channels (Austin, Tex.) · 2023Review
- Structural basis of the activation of TRPV5 channels by long-chain acyl-Coenzyme-A.Nature communications · 2023Article
- Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin.Nature communications · 2023Article
- Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein.Nature communications · 2023Article
- Review
- TRPV6 Regulation by Cis-22a and Cholesterol.Biomolecules · 2022Article
- Calcium selective channel TRPV6: Structure, function, and implications in health and disease.Gene · 2022Review
- Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole.Nature communications · 2021Article
- Structure and function of the calcium-selective TRP channel TRPV6.The Journal of physiology · 2021Review
- Methods to study phosphoinositide regulation of ion channels.Methods in enzymology · 2021Article
- Article
- Activation of the calcium sensing receptor attenuates TRPV6-dependent intestinal calcium absorption.JCI insight · 2019Article
- Depletion of plasma membrane-associated phosphoinositides mimics inhibition of TRPM7 channels by cytosolic MgThe Journal of biological chemistry · 2018Article
- Structural insights on TRPV5 gating by endogenous modulators.Nature communications · 2018Article
- PIPeLife · 2018Article
- Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Transient receptor potential vanilloid 6 (TRPV6) channels play an important role in Ca(2+) absorption in the intestines. Both phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] and cytoplasmic ATP have been proposed to be important for maintaining TRPV6 activity. To evaluate whether PtdIns(4,5)P(2) and ATP affect channel activity directly or indirectly, we have used a dual approach, examining channel activity in excised patches and planar lipid bilayers. In excised inside-out patch-clamp measurements, ATP reactivated the human TRPV6 channels after current rundown only in the presence of Mg(2+). The effect of MgATP was inhibited by 3 structurally different compounds that inhibit type III phosphatidylinositol 4-kinases (PI4Ks). PtdIns(4,5)P(2) also activated TRPV6 in excised patches, while its precursor PtdIns(4)P had only minimal effect. These data demonstrate that MgATP provides substrate for lipid kinases, allowing the resynthesis of PtdIns(4,5)P(2). To determine whether PtdIns(4,5)P(2) is a direct activator of TRPV6, we purified and reconstituted the channel protein in planar lipid bilayers. The reconstituted channel showed high activity in the presence of PtdIns(4,5)P(2), while PtdIns(4)P induced only minimal activity. Our data establish PtdIns(4,5)P(2) as a direct activator of TRPV6 and demonstrate that intracellular ATP regulates the channel indirectly as a substrate for type III PI4Ks.
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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.