Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
FASEB J
2011 Nov 01;2511:3915-28. doi: 10.1096/fj.11-184630.
Show Gene links
Show Anatomy links
Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5) P₂.
Zakharian E
,
Cao C
,
Rohacs T
.
???displayArticle.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.
Akey,
TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations.
2006, Pubmed
Akey,
TRPV6 exhibits unusual patterns of polymorphism and divergence in worldwide populations.
2006,
Pubmed
Al-Ansary,
ATP modulates Ca2+ uptake by TRPV6 and is counteracted by isoform-specific phosphorylation.
2010,
Pubmed
Balla,
Phosphatidylinositol 4-kinases: old enzymes with emerging functions.
2006,
Pubmed
Balla,
Design of drug-resistant alleles of type-III phosphatidylinositol 4-kinases using mutagenesis and molecular modeling.
2008,
Pubmed
Balla,
Pharmacology of phosphoinositides, regulators of multiple cellular functions.
2001,
Pubmed
Bianco,
Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene.
2007,
Pubmed
Clapham,
Calcium signaling.
2007,
Pubmed
D'Avanzo,
Direct and specific activation of human inward rectifier K+ channels by membrane phosphatidylinositol 4,5-bisphosphate.
2010,
Pubmed
Daniels,
Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate.
2009,
Pubmed
,
Xenbase
Derler,
Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+-dependent inactivation.
2006,
Pubmed
Grycova,
ATP binding site on the C-terminus of the vanilloid receptor.
2007,
Pubmed
Hilgemann,
The complex and intriguing lives of PIP2 with ion channels and transporters.
2001,
Pubmed
Hilgemann,
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
1996,
Pubmed
Hilgemann,
Cytoplasmic ATP-dependent regulation of ion transporters and channels: mechanisms and messengers.
1997,
Pubmed
Hoenderop,
Calcium absorption across epithelia.
2005,
Pubmed
Hoenderop,
Function and expression of the epithelial Ca(2+) channel family: comparison of mammalian ECaC1 and 2.
2001,
Pubmed
Hoenderop,
Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5.
2003,
Pubmed
Hughes,
Parallel selection on TRPV6 in human populations.
2008,
Pubmed
Knight,
A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.
2006,
Pubmed
Korzeniowski,
Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides.
2009,
Pubmed
Kwak,
Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains.
2000,
Pubmed
,
Xenbase
Leal-Pinto,
Gating of a G protein-sensitive mammalian Kir3.1 prokaryotic Kir channel chimera in planar lipid bilayers.
2010,
Pubmed
,
Xenbase
Lishko,
The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
2007,
Pubmed
Liu,
Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate.
2005,
Pubmed
Logothetis,
Dynamic changes in phosphoinositide levels control ion channel activity.
2007,
Pubmed
Lukacs,
Dual regulation of TRPV1 by phosphoinositides.
2007,
Pubmed
,
Xenbase
Mercado,
Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate.
2010,
Pubmed
Murata,
Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2.
2007,
Pubmed
,
Xenbase
Nakanishi,
A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids.
1995,
Pubmed
Niemeyer,
Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin.
2001,
Pubmed
Nilius,
Transient receptor potential cation channels in disease.
2007,
Pubmed
Nilius,
Transient receptor potential channels meet phosphoinositides.
2008,
Pubmed
Nilius,
Transient receptor potential channelopathies.
2010,
Pubmed
O'Rourke,
Ion channels as sensors of cellular energy. Mechanisms for modulation by magnesium and nucleotides.
1993,
Pubmed
Phelps,
Structural analyses of the ankyrin repeat domain of TRPV6 and related TRPV ion channels.
2008,
Pubmed
Phelps,
Differential regulation of TRPV1, TRPV3, and TRPV4 sensitivity through a conserved binding site on the ankyrin repeat domain.
2010,
Pubmed
Rohacs,
Phosphoinositide regulation of non-canonical transient receptor potential channels.
2009,
Pubmed
Rohács,
PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain.
2005,
Pubmed
Rohács,
Assaying phosphatidylinositol bisphosphate regulation of potassium channels.
2002,
Pubmed
,
Xenbase
Suchyna,
Biophysics and structure of the patch and the gigaseal.
2009,
Pubmed
Suh,
PIP2 is a necessary cofactor for ion channel function: how and why?
2008,
Pubmed
Suzuki,
Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation.
2008,
Pubmed
,
Xenbase
Thyagarajan,
Hydrolysis of phosphatidylinositol 4,5-bisphosphate mediates calcium-induced inactivation of TRPV6 channels.
2008,
Pubmed
Thyagarajan,
Phospholipase C-mediated regulation of transient receptor potential vanilloid 6 channels: implications in active intestinal Ca2+ transport.
2009,
Pubmed
Tominaga,
Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia.
2001,
Pubmed
Tóth,
Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi.
2006,
Pubmed
Tóth,
Identification of direct and indirect effectors of the transient receptor potential melastatin 2 (TRPM2) cation channel.
2010,
Pubmed
,
Xenbase
Voets,
Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6.
2003,
Pubmed
Wu,
International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family.
2010,
Pubmed
Yao,
Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor.
2009,
Pubmed
Yue,
CaT1 manifests the pore properties of the calcium-release-activated calcium channel.
2001,
Pubmed
Zakharian,
Inorganic polyphosphate modulates TRPM8 channels.
2009,
Pubmed
Zakharian,
Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers.
2010,
Pubmed
