Skip to main content

Regulation of TRP Ion Channels by Phosphatidylinositol-4,5-Bisphosphate

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 179))

Abstract

Phosphatidylinositol-4,5-bisphosphate (PIP2) has emerged as a versatile regulator of TRP ion channels. In many cases, the regulation involves interactions of channel proteins with the lipid itself independent of its hydrolysis products. The functions of the regulation mediated by such interactions are diverse. Some TRP channels absolutely require PIP2 for functioning, while others are inhibited. A change of gating is common to all, endowing the lipid a role for modulation of the sensitivity of the channels to their physiological stimuli. The activation of TRP channels may also influence cellular PIP2 levels via the influx of Ca2+ through these channels. Depletion of PIP2 in the plasma membrane occurs upon activation of TRPV1, TRPM8, and possibly TRPM4/5 in heterologous expression systems, whereas resynthesis of PIP2 requires Ca2+ entry through the TRP/TRPL channels in Drosophila photoreceptors. These developments concerning PIP2 regulation of TRP channels reinforce the significance of the PLC signaling cascade in TRP channel function, and provide further perspectives for understanding the physiological roles of these ubiquitous and often enigmatic channels.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   429.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agam K, von Campenhausen M, Levy S, Ben-Ami HC, Cook B, Kirschfeld K, Minke B (2000) Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP and TRPL in vivo. J Neurosci 20:5748–5755

    PubMed  CAS  Google Scholar 

  • Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857

    Article  PubMed  CAS  Google Scholar 

  • Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321

    Article  PubMed  CAS  Google Scholar 

  • Bloomquist BT, Shortridge RD, Schneuwly S, Perdew M, Montell C, Steller H, Rubin G, Pak WL (1988) Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction. Cell 54:723–733

    Article  PubMed  CAS  Google Scholar 

  • Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655–1657

    Article  PubMed  CAS  Google Scholar 

  • Cesare P, McNaughton P (1996) A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc Natl Acad Sci U S A 93:15435–15439

    Article  PubMed  CAS  Google Scholar 

  • Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957–962

    Article  PubMed  CAS  Google Scholar 

  • Corey DP, Garcia-Anoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Geleoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, Zhang DS (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432:723–730

    Article  PubMed  CAS  Google Scholar 

  • Cullen PJ, Cozier GE, Banting G, Mellor H (2001) Modular phosphoinositide-binding domains—their role in signalling and membrane trafficking. Curr Biol 11:R882–R893

    Article  PubMed  CAS  Google Scholar 

  • del Pilar Gomez M, Nasi E (2005) A direct signaling role for phosphatidylinositol 4,5-bisphosphate (PIP2) in the visual excitation process of microvillar receptors. J Biol Chem 280:16784–16789

    Article  PubMed  CAS  Google Scholar 

  • Dennis EA (1994) Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem 269:13057–13060

    PubMed  CAS  Google Scholar 

  • Estacion M, Sinkins WG, Schilling WP (2001) Regulation of Drosophila transient receptor potential-like (TrpL) channels by phospholipase C-dependent mechanisms. J Physiol 530:1–19

    Article  PubMed  CAS  Google Scholar 

  • Exton JH (1997) Phospholipase D: enzymology, mechanisms of regulation, and function. Physiol Rev 77:303–320

    PubMed  CAS  Google Scholar 

  • Gambhir A, Hangyas-Mihalyne G, Zaitseva I, Cafiso DS, Wang J, Murray D, Pentyala SN, Smith SO, McLaughlin S (2004) Electrostatic sequestration of PIP2 on phospholipids membranes by basic/aromatic regions of proteins. Biophys J 86:2188–2207

    PubMed  CAS  Google Scholar 

  • Hardie RC (2003) Regulation of TRP channels via lipid second messengers. Annu Rev Physiol 65:735–759

    Article  PubMed  CAS  Google Scholar 

  • Hardie RC, Raghu P, Moore S, Juusola M, Baines RA, Sweeney ST (2001) Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors. Neuron 30:149–159

    Article  PubMed  CAS  Google Scholar 

  • Hardie RC, Gu Y, Martin F, Sweeney ST, Raghu P (2004) In vivo light-induced and basal phospholipase C activity in Drosophila photoreceptors measured with genetically targeted phosphatidylinositol 4,5-bisphosphate-sensitive ion channels (Kir2.1). J Biol Chem 279:47773–47782

    Article  PubMed  CAS  Google Scholar 

  • Harteneck C, Plant TD, Schultz G (2000) From worm to man: three subfamilies of TRP channels. Trends Neurosci 23:159–166

    Article  PubMed  CAS  Google Scholar 

  • Hilgemann DW (1997) Cytoplasmic ATP-dependent regulation of ion transporters and channels: mechanisms and messengers. Annu Rev Physiol 59:193–220

    Article  PubMed  CAS  Google Scholar 

  • Hilgemann DW, Ball R (1996) Regulation of cardiac Na+, Ca2+ exchange and KATP potassium channels by PIP2. Science 2735277:956–959

    Article  PubMed  CAS  Google Scholar 

  • Hilgemann DW, Feng S, Nasuhoglu C (2001) The complex and intriguing lives of PIP2 with ion channels and transporters. Sci STKE 2001:RE19

    Google Scholar 

  • Hinchliffe K, Irvine R (1997) Inositol lipid pathways turn turtle. Nature 390:123–124

    Article  PubMed  CAS  Google Scholar 

  • Hirono M, Denis CS, Richardson GP, Gillespie PG (2004) Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation. Neuron 44:309–320

    Article  PubMed  CAS  Google Scholar 

  • Hirose K, Kadowaki S, Tanabe M, Takeshima H, Iino M (1999) Spatiotemporal dynamics of inositol 1,4,5-trisphosphate that underlies complex Ca2+ mobilization patterns. Science 284:1527–1530

    Article  PubMed  CAS  Google Scholar 

  • Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ (2003) Homo-and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6. EMBO J 22:776–785

    Article  PubMed  CAS  Google Scholar 

  • Horowitz LF, Hirdes W, Suh BC, Hilgemann DW, Mackie K, Hille B (2005) Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current. J Gen Physiol 126:243–262

    Article  PubMed  CAS  Google Scholar 

  • Huang CL, Feng S, Hilgemann DW (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature 3919:803–806

    Article  Google Scholar 

  • Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265

    Article  PubMed  CAS  Google Scholar 

  • Khasar SG, McCarter G, Levine JD (1999) Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J Neurophysiol 81:1104–1112

    PubMed  CAS  Google Scholar 

  • Lassing I, Lindberg U (1985) Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin. Nature 314:472–474

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Cha SK, Sun TJ, Huang CL (2005) PIP2 activates TRPV5 and releases its inhibition by intracellular Mg2+. J Gen Physiol 126:439–451

    Article  PubMed  CAS  Google Scholar 

  • Lemmon MA, Ferguson KM (2000) Signal-dependent membrane targeting by pleckstrin homology (PH) domains. Biochem J 350:1–18

    Article  PubMed  CAS  Google Scholar 

  • Liu B, Qin F (2005) Functional control of cold-and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J Neurosci 25:1674–1681

    Article  PubMed  CAS  Google Scholar 

  • Liu B, Zhang C, Qin F (2005) Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. J Neurosci 25:4835–4843

    Article  PubMed  CAS  Google Scholar 

  • Liu D, Liman ER (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc Natl Acad Sci U S A 100:15160–15165

    Article  PubMed  CAS  Google Scholar 

  • Majerus PW, Kisseleva MV, Norris FA (1999) The role of phosphatases in inositol signaling reactions. J Biol Chem 274:10669–10672

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin S, Wang J, Gambhir A, Murray D (2002) PIP(2) and proteins: interactions, organization, and information flow. Annu Rev Biophys Biomol Struct 31:151–175

    Article  PubMed  CAS  Google Scholar 

  • Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323

    Article  PubMed  CAS  Google Scholar 

  • Nagata K, Duggan A, Kumar G, Garcia-Anoveros J (2005) Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J Neurosci 25:4052–4061

    Article  PubMed  CAS  Google Scholar 

  • Nilius B, Vennekens R, Prenen J, Hoenderop JG, Droogmans G, Bindels RJ (2001) The single pore residue Asp542 determines Ca2+ permeation and Mg2+ block of the epithelial Ca2+ channel. J Biol Chem 276:1020–1025

    Article  PubMed  CAS  Google Scholar 

  • Prescott ED, Julius D (2003) A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:1284–1288

    Article  PubMed  CAS  Google Scholar 

  • Rameh LE, Tolias KF, Duckworth BC, Cantley LC (1997) A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate. Nature 390:192–196

    Article  PubMed  CAS  Google Scholar 

  • Rebecchi MJ, Scarlata S (1998) Pleckstrin homology domains: a common fold with diverse functions. Annu Rev Biophys Biomol Struct 27:503–528

    Article  PubMed  CAS  Google Scholar 

  • Reid G, Flonta ML (2002) Ion channels activated by cold and menthol in cultured rat dorsal root ganglion neurones. Neurosci Lett 324:164–168

    Article  PubMed  CAS  Google Scholar 

  • Rhee SG (2001) Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 70:281–312

    Article  PubMed  CAS  Google Scholar 

  • Rohacs T, Lopes CM, Michailidis I, Logothetis DE (2005) PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat Neurosci 8:626–634

    Article  PubMed  CAS  Google Scholar 

  • Runnels LW, Yue L, Clapham DE (2002) The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol 4:329–336

    PubMed  CAS  Google Scholar 

  • Scott K, Zuker C (1998) TRP, TRPL and trouble in photoreceptor cells. Curr Opin Neurobiol 8:383–388

    Article  PubMed  CAS  Google Scholar 

  • Shu X, Mendell LM (2001) Acute sensitization by NGF of the response of small-diameter sensory neurons to capsaicin. J Neurophysiol 86:2931–2938

    PubMed  CAS  Google Scholar 

  • Suh BC, Hille B (2005) Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate. Curr Opin Neurobiol 15:370–378

    Article  PubMed  CAS  Google Scholar 

  • Szallasi A, Blumberg PM (1999) Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51:159–212

    PubMed  CAS  Google Scholar 

  • Tolias KF, Carpenter CL (2000) Enzymes involved in the synthesis of PI(4,5)P2 and their regulation: PI kinases and PIP kinases. In: Cockcroft S (ed) Biology of phosphoinositides. Oxford University Press, Oxford

    Google Scholar 

  • van Rossum DB, Patterson RL, Sharma S, Barrow RK, Kornberg M, Gill DL, Snyder SH (2005) Phospholipase Cgamma1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 434:99–104

    Article  PubMed  CAS  Google Scholar 

  • Varnai P, Balla T (1998) Visualization of phosphoinositides that bind pleckstrin homology domains: calcium-and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools. J Cell Biol 143:501–510

    Article  PubMed  CAS  Google Scholar 

  • Vazquez G, Wedel BJ, Aziz O, Trebak M, Putney JW Jr (2004) The mammalian TRPC cation channels. Biochim Biophys Acta 1742:21–36

    Article  PubMed  CAS  Google Scholar 

  • Voets T, Janssens A, Prenen J, Droogmans G, Nilius B (2003) Mg2+-dependent gating and strong inward rectification of the cation channel TRPV6. J Gen Physiol 121:245–260

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Gambhir A, McLaughlin S, Murray D (2004) A computational model for the electrostatic sequestration of PI(4,5)P2 by membrane-adsorbed basic peptides. Biophys J 86:1969–1986

    Article  PubMed  CAS  Google Scholar 

  • Woscholski R, Parker PJ (1997) Inositol lipid 5-phosphatases—traffic signals and signal traffic. Trends Biochem Sci 22:427–431

    Article  PubMed  CAS  Google Scholar 

  • Yeh BI, Sun TJ, Lee JZ, Chen HH, Huang CL (2003) Mechanism and molecular determinant for regulation of rabbit transient receptor potential type 5 (TRPV5) channel by extracellular pH. J Biol Chem 278:51044–51052

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Huang J, McNaughton PA (2005a) NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24:4211–4223

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Okawa H, Wang Y, Liman ER (2005b) Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from desensitization. J Biol Chem 280:39185–39192

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Qin, F. (2007). Regulation of TRP Ion Channels by Phosphatidylinositol-4,5-Bisphosphate. In: Flockerzi, V., Nilius, B. (eds) Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology, vol 179. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-34891-7_30

Download citation

Publish with us

Policies and ethics