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.
J Biol Chem
2013 Dec 06;28849:35003-13. doi: 10.1074/jbc.M113.520288.
Show Gene links
Show Anatomy links
Promiscuous activation of transient receptor potential vanilloid 1 (TRPV1) channels by negatively charged intracellular lipids: the key role of endogenous phosphoinositides in maintaining channel activity.
Lukacs V
,
Rives JM
,
Sun X
,
Zakharian E
,
Rohacs T
.
???displayArticle.abstract???
The regulation of the heat- and capsaicin-activated transient receptor potential vanilloid 1 (TRPV1) channels by phosphoinositides is controversial. Data in cellular systems support the dependence of TRPV1 activity on phosphoinositides. The purified TRPV1, however, was recently shown to be fully functional in artificial liposomes in the absence of phosphoinositides. Here, we show that several other negatively charged phospholipids, including phosphatidylglycerol, can also support TRPV1 activity in excised patches at high concentrations. When we incorporated TRPV1 into planar lipid bilayers consisting of neutral lipids, capsaicin-induced activity depended on phosphatidylinositol 4,5-bisphosphate. We also found that TRPV1 activity in excised patches ran down and that MgATP reactivated the channel. Inhibition of phosphatidylinositol 4-kinases or enzymatic removal of phosphatidylinositol abolished this effect of MgATP, suggesting that it activated TRPV1 by generating endogenous phosphoinositides. We conclude that endogenous phosphoinositides are positive cofactors for TRPV1 activity. Our data highlight the importance of specificity in lipid regulation of ion channels and may reconcile discordant data obtained in various experimental settings.
Brauchi,
Dissection of the components for PIP2 activation and thermosensation in TRP channels.
2007, Pubmed
Brauchi,
Dissection of the components for PIP2 activation and thermosensation in TRP channels.
2007,
Pubmed
Cao,
TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids.
2013,
Pubmed
Chuang,
Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.
2001,
Pubmed
,
Xenbase
De Petrocellis,
Overlap between the ligand recognition properties of the anandamide transporter and the VR1 vanilloid receptor: inhibitors of anandamide uptake with negligible capsaicin-like activity.
2000,
Pubmed
Du,
Characteristic interactions with phosphatidylinositol 4,5-bisphosphate determine regulation of kir channels by diverse modulators.
2004,
Pubmed
,
Xenbase
El-Arabi,
Ion channel drug potency assay with an artificial bilayer chip.
2012,
Pubmed
Fan,
Anionic phospholipids activate ATP-sensitive potassium channels.
1997,
Pubmed
Gamper,
Phosphoinositide sensitivity of ion channels, a functional perspective.
2012,
Pubmed
Gamper,
Regulation of ion transport proteins by membrane phosphoinositides.
2007,
Pubmed
Hammond,
PI4P and PI(4,5)P2 are essential but independent lipid determinants of membrane identity.
2012,
Pubmed
Hansen,
Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2.
2011,
Pubmed
Hilgemann,
Fitting K(V) potassium channels into the PIP(2) puzzle: Hille group connects dots between illustrious HH groups.
2012,
Pubmed
Hilgemann,
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
1996,
Pubmed
Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase
Hui,
Capsaicin activation of the pain receptor, VR1: multiple open states from both partial and full binding.
2003,
Pubmed
,
Xenbase
Imai,
A self-limiting regulation of vasoconstrictor-activated TRPC3/C6/C7 channels coupled to PI(4,5)P₂-diacylglycerol signalling.
2012,
Pubmed
Jeske,
A-kinase anchoring protein 150 mediates transient receptor potential family V type 1 sensitivity to phosphatidylinositol-4,5-bisphosphate.
2011,
Pubmed
Kim,
Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1.
2008,
Pubmed
Klein,
Determinants of molecular specificity in phosphoinositide regulation. Phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is the endogenous lipid regulating TRPV1.
2008,
Pubmed
Krauter,
Phospholipids as modulators of K(ATP) channels: distinct mechanisms for control of sensitivity to sulphonylureas, K(+) channel openers, and ATP.
2001,
Pubmed
,
Xenbase
Kwak,
Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains.
2000,
Pubmed
,
Xenbase
Lemonnier,
Complex regulation of the TRPC3, 6 and 7 channel subfamily by diacylglycerol and phosphatidylinositol-4,5-bisphosphate.
2008,
Pubmed
Lishko,
The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
2007,
Pubmed
Liu,
Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5.
2003,
Pubmed
Liu,
Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate.
2005,
Pubmed
Logothetis,
Phosphoinositide-mediated gating of inwardly rectifying K(+) channels.
2007,
Pubmed
Lukacs,
Distinctive changes in plasma membrane phosphoinositides underlie differential regulation of TRPV1 in nociceptive neurons.
2013,
Pubmed
,
Xenbase
Lukacs,
Dual regulation of TRPV1 by phosphoinositides.
2007,
Pubmed
,
Xenbase
Nilius,
Transient receptor potential channels meet phosphoinositides.
2008,
Pubmed
Nilius,
The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate.
2006,
Pubmed
Ohtsuka,
A somatic cell mutant defective in phosphatidylglycerophosphate synthase, with impaired phosphatidylglycerol and cardiolipin biosynthesis.
1993,
Pubmed
Patil,
Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses.
2011,
Pubmed
Prescott,
A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity.
2003,
Pubmed
,
Xenbase
Raisinghani,
Activation of transient receptor potential vanilloid 1 (TRPV1) by resiniferatoxin.
2005,
Pubmed
,
Xenbase
Rohacs,
Phosphoinositide regulation of TRP channels.
2014,
Pubmed
Rohacs,
Phospholipase C mediated modulation of TRPV1 channels.
2008,
Pubmed
Rohacs,
Regulation of transient receptor potential channels by the phospholipase C pathway.
2013,
Pubmed
Rohács,
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.
2003,
Pubmed
,
Xenbase
Rohács,
PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain.
2005,
Pubmed
Runnels,
The TRPM7 channel is inactivated by PIP(2) hydrolysis.
2002,
Pubmed
Stein,
Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane.
2006,
Pubmed
Suh,
PIP2 is a necessary cofactor for ion channel function: how and why?
2008,
Pubmed
Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase
Thyagarajan,
Hydrolysis of phosphatidylinositol 4,5-bisphosphate mediates calcium-induced inactivation of TRPV6 channels.
2008,
Pubmed
Trebak,
Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels.
2009,
Pubmed
Ufret-Vincenty,
Localization of the PIP2 sensor of TRPV1 ion channels.
2011,
Pubmed
Vance,
Metabolism and functions of phosphatidylserine.
2005,
Pubmed
Woo,
Direct activation of transient receptor potential vanilloid 1(TRPV1) by diacylglycerol (DAG).
2008,
Pubmed
Yao,
Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor.
2009,
Pubmed
Yudin,
Decrease in phosphatidylinositol 4,5-bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels.
2011,
Pubmed
Zakharian,
Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5) P₂.
2011,
Pubmed
,
Xenbase
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
Zygmunt,
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide.
1999,
Pubmed
,
Xenbase
