Skip to main content
SpringerLink
Log in

Phosphoinositide Regulation of TRP Channels

  • Chapter
  • First Online:
Mammalian Transient Receptor Potential (TRP) Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 223))

Abstract

Transient Receptor Potential (TRP) channels are activated by stimuli as diverse as heat, cold, noxious chemicals, mechanical forces, hormones, neurotransmitters, spices, and voltage. Besides their presumably similar general architecture, probably the only common factor regulating them is phosphoinositides. The regulation of TRP channels by phosphoinositides is complex. There are a large number of TRP channels where phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2 or PIP2] acts as a positive cofactor, similarly to many other ion channels. In several cases, however, PI(4,5)P2 inhibits TRP channel activity, sometimes even concurrently with the activating effect. This chapter will provide a comprehensive overview of the literature on regulation of TRP channels by membrane phosphoinositides.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Institutional subscriptions

Abbreviations

AASt:

Arachydonyl-stearyl

AKAP:

A-kinase anchoring protein

DAG:

Diacylglycerol

DGS-NTA:

1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl)iminodiacetic acid)succinyl]

DRG:

Dorsal root ganglion

ER:

Endoplasmic reticulum

GPCR:

G Protein Coupled Receptor

IP3 :

Inositol-1,4,5-trisphopshate

Kir:

K+ inwardly rectifying

PI:

Phosphatidylinositol

PI(4)P:

Phosphatidylinositol 4-phosphate

PI(4,5)P2 :

Phosphatidylinositol 4,5-bisphosphate

PI4K:

Phosphatidylinositol 4-kinase

PIP5K:

Phosphatidylinositol 4-phosphate 5-kinase

PI3K:

Phosphoinositide 3-kinase

PLC:

Phospholipase C

PG:

Phosphatidyl glycerol

PKC:

Protein Kinase C

PH:

Pleckstrin-homology

Pirt:

Phosphoinositide interacting regulator of TRP

PM:

Plasma membrane

TG:

Trigeminal ganglion

TPC:

Two-pore channel

TRP:

Transient Receptor Potential

TRPA:

TRP Ankyrin

TRPC:

TRP Classical

TRPL:

TRP-like

TRPM:

TRP Melastatin

TRPML:

TRP Mucolipin

TRPP:

TRP Polycystin

TRPV:

TRP Vanilloid

VSP:

Voltage sensitive phosphatase

References

  • Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM (2007) Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol 583:175–193

    CAS  PubMed Central  PubMed  Google Scholar 

  • Albert AP, Saleh SN, Large WA (2008) Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes. J Physiol 586:3087–3095

    CAS  PubMed Central  PubMed  Google Scholar 

  • Allen V, Swigart P, Cheung R, Cockcroft S, Katan M (1997) Regulation of inositol lipid-specific phospholipase C-delta by changes in Ca2+ ion concentrations. Biochem J 327:545–552

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baukrowitz T, Schulte U, Oliver D, Herlitze S, Krauter T, Tucker SJ, Ruppersberg JP, Fakler B (1998) PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282:1141–1144

    CAS  PubMed  Google Scholar 

  • Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D (2007) The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448:204–208

    CAS  PubMed  Google Scholar 

  • Bianco SD, Peng JB, Takanaga H, Suzuki Y, Crescenzi A, Kos CH, Zhuang L, Freeman MR, Gouveia CH, Wu J, Luo H, Mauro T, Brown EM, Hediger MA (2007) Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J Bone Miner Res 22:274–285

    CAS  PubMed  Google Scholar 

  • Bojjireddy N, Botyanszki J, Hammond G, Creech D, Peterson R, Kemp DC, Snead M, Brown R, Morrison A, Wilson S, Harrison S, Moore C, Balla T (2014) Pharmacological and Genetic Targeting of the PI4KA Enzyme Reveals Its Important Role in Maintaining Plasma Membrane Phosphatidylinositol 4-Phosphate and Phosphatidylinositol 4,5-Bisphosphate Levels. J Biol Chem 289:6120–6132

    CAS  PubMed  Google Scholar 

  • Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H, Rosenmann E, Gonzalez-Nilo F, Latorre R (2007) Dissection of the components for PIP2 activation and thermosensation in TRP channels. Proc Natl Acad Sci U S A 104:10246–10251

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cao C, Zakharian E, Borbiro I, Rohacs T (2013a) Interplay between calmodulin and phosphatidylinositol 4,5-bisphosphate in Ca2+-induced inactivation of transient receptor potential vanilloid 6 channels. J Biol Chem 288:5278–5290

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D (2013b) TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron 77:667–679

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng WW, D’Avanzo N, Doyle DA, Nichols CG (2011) Dual-mode phospholipid regulation of human inward rectifying potassium channels. Biophys J 100:620–628

    CAS  PubMed Central  PubMed  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

    CAS  PubMed  Google Scholar 

  • D’Avanzo N, Cheng WW, Doyle DA, Nichols CG (2010) Direct and specific activation of human inward rectifier K+ channels by membrane phosphatidylinositol 4,5-bisphosphate. J Biol Chem 285:37129–37132

    PubMed Central  PubMed  Google Scholar 

  • Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, Kobayashi K, Obata K, Yamanaka H, Noguchi K (2007) Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 117:1979–1987

    CAS  PubMed Central  PubMed  Google Scholar 

  • Daniels RL, Takashima Y, McKemy DD (2009) Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate. J Biol Chem 284:1570–1582

    CAS  PubMed Central  PubMed  Google Scholar 

  • de Groot T, Kovalevskaya NV, Verkaart S, Schilderink N, Felici M, van der Hagen EA, Bindels RJ, Vuister GW, Hoenderop JG (2011) Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone. Mol Cell Biol 31:2845–2853

    PubMed Central  PubMed  Google Scholar 

  • Derler I, Hofbauer M, Kahr H, Fritsch R, Muik M, Kepplinger K, Hack ME, Moritz S, Schindl R, Groschner K, Romanin C (2006) Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+-dependent inactivation. J Physiol 577:31–44

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A (2007) TRPM8 is required for cold sensation in mice. Neuron 54:371–378

    CAS  PubMed  Google Scholar 

  • DiNitto JP, Cronin TC, Lambright DG (2003) Membrane recognition and targeting by lipid-binding domains. Sci STKE 2003:re16

    PubMed  Google Scholar 

  • Doerner JF, Hatt H, Ramsey IS (2011) Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4,5)P2 hydrolysis. J Gen Physiol 137:271–288

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dong XP, Shen D, Wang X, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman LS, Delling M, Xu H (2010) PI(3,5)P2 controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome. Nat Commun 1:38

    PubMed Central  PubMed  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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fan Z, Makielski JC (1997) Anionic phospholipids activate ATP-sensitive potassium channels. J Biol Chem 272:5388–5395

    CAS  PubMed  Google Scholar 

  • Fruman DA, Meyers RE, Cantley LC (1998) Phosphoinositide kinases. Annu Rev Biochem 67:481–507

    CAS  PubMed  Google Scholar 

  • Fujita F, Uchida K, Takaishi M, Sokabe T, Tominaga M (2013) Ambient temperature affects the temperature threshold for TRPM8 activation through interaction of phosphatidylinositol 4,5-bisphosphate. J Neurosci 33:6154–6159

    CAS  PubMed  Google Scholar 

  • Fukami K, Inanobe S, Kanemaru K, Nakamura Y (2010) Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance. Prog Lipid Res 49:429–437

    CAS  PubMed  Google Scholar 

  • Furukawa T, Yamane T, Terai T, Katayama Y, Hiraoka M (1996) Functional linkage of the cardiac ATP-sensitive K+ channel to the actin cytoskeleton. Pflugers Arch 431:504–512

    CAS  PubMed  Google Scholar 

  • Gamper N, Rohacs T (2012) Phosphoinositide sensitivity of ion channels, a functional perspective. Subcell Biochem 59:289–333

    CAS  PubMed  Google Scholar 

  • Garcia-Elias A, Mrkonjic S, Pardo-Pastor C, Inada H, Hellmich UA, Rubio-Moscardo F, Plata C, Gaudet R, Vicente R, Valverde MA (2013) Phosphatidylinositol-4,5-biphosphate-dependent rearrangement of TRPV4 cytosolic tails enables channel activation by physiological stimuli. Proc Natl Acad Sci U S A 110:9553–9558

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gwanyanya A, Sipido KR, Vereecke J, Mubagwa K (2006) ATP and PIP2 dependence of the magnesium-inhibited, TRPM7-like cation channel in cardiac myocytes. Am J Physiol Cell Physiol 291:C627–635

    CAS  PubMed  Google Scholar 

  • Hammond GR, Fischer MJ, Anderson KE, Holdich J, Koteci A, Balla T, Irvine RF (2012) PI4P and PI(4,5)P2 are essential but independent lipid determinants of membrane identity. Science 337:727–730

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hansen SB, Tao X, MacKinnon R (2011) Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2. Nature 477:495–498

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hardie RC (2007) TRP channels and lipids: from Drosophila to mammalian physiology. J Physiol 578:9–24

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hilgemann DW (2012) Fitting K(V) potassium channels into the PIP2 puzzle: Hille group connects dots between illustrious HH groups. J Gen Physiol 140:245–248

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hilgemann DW, Ball R (1996) Regulation of cardiac Na+, Ca2+ exchange and KATP potassium channels by PIP2. Science 273:956–959

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Hoenderop JG, van Leeuwen JP, van der Eerden BC, Kersten FF, van der Kemp AW, Merillat AM, Waarsing JH, Rossier BC, Vallon V, Hummler E, Bindels RJ (2003) Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5. J Clin Invest 112:1906–1914

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang CL (2007) Complex roles of PIP2 in the regulation of ion channels and transporters. Am J Physiol Renal Physiol 293:F1761–1765

    CAS  PubMed  Google Scholar 

  • Huang CL, Feng S, Hilgemann DW (1998) Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma. Nature 391:803–806

    CAS  PubMed  Google Scholar 

  • Huang J, Liu CH, Hughes SA, Postma M, Schwiening CJ, Hardie RC (2010) Activation of TRP channels by protons and phosphoinositide depletion in Drosophila photoreceptors. Curr Biol 20:189–197

    CAS  PubMed  Google Scholar 

  • Imai Y, Itsuki K, Okamura Y, Inoue R, Mori MX (2012) A self-limiting regulation of vasoconstrictor-activated TRPC3/C6/C7 channels coupled to PI(4,5)P2-diacylglycerol signalling. J Physiol 590:1101–1119

    CAS  PubMed Central  PubMed  Google Scholar 

  • Itsuki K, Imai Y, Okamura Y, Abe K, Inoue R, Mori MX (2012) Voltage-sensing phosphatase reveals temporal regulation of TRPC3/C6/C7 channels by membrane phosphoinositides. Channels (Austin) 6:206–209

    CAS  Google Scholar 

  • Jardin I, Redondo PC, Salido GM, Rosado JA (2008) Phosphatidylinositol 4,5-bisphosphate enhances store-operated calcium entry through hTRPC6 channel in human platelets. Biochim Biophys Acta 1783:84–97

    CAS  PubMed  Google Scholar 

  • Jeske NA, Por ED, Belugin S, Chaudhury S, Berg KA, Akopian AN, Henry MA, Gomez R (2011) A-kinase anchoring protein 150 mediates transient receptor potential family V type 1 sensitivity to phosphatidylinositol-4,5-bisphosphate. J Neurosci 31:8681–8688

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jin J, Wu LJ, Jun J, Cheng X, Xu H, Andrews NC, Clapham DE (2012) The channel kinase, TRPM7, is required for early embryonic development. Proc Natl Acad Sci U S A 109:E225–233

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ju M, Shi J, Saleh SN, Albert AP, Large WA (2010) Ins(1,4,5)P3 interacts with PIP2 to regulate activation of TRPC6/C7 channels by diacylglycerol in native vascular myocytes. J Physiol 588:1419–1433

    CAS  PubMed Central  PubMed  Google Scholar 

  • Karashima Y, Prenen J, Meseguer V, Owsianik G, Voets T, Nilius B (2008) Modulation of the transient receptor potential channel TRPA1 by phosphatidylinositol 4,5-biphosphate manipulators. Pflugers Arch 457:77–89

    CAS  PubMed  Google Scholar 

  • Kim D, Cavanaugh EJ (2007) Requirement of a soluble intracellular factor for activation of transient receptor potential A1 by pungent chemicals: role of inorganic polyphosphates. J Neurosci 27:6500–6509

    CAS  PubMed  Google Scholar 

  • Kim AY, Tang Z, Liu Q, Patel KN, Maag D, Geng Y, Dong X (2008a) Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1. Cell 133:475–485

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim BJ, Kim MT, Jeon JH, Kim SJ, So I (2008b) Involvement of phosphatidylinositol 4,5-bisphosphate in the desensitization of canonical transient receptor potential 5. Biol Pharm Bull 31:1733–1738

    CAS  PubMed  Google Scholar 

  • Kim D, Cavanaugh EJ, Simkin D (2008c) Inhibition of transient receptor potential A1 channel by phosphatidylinositol-4,5-bisphosphate. Am J Physiol Cell Physiol 295:C92–99

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim H, Jeon JP, Hong C, Kim J, Myeong J, Jeon JH, So I (2013) An essential role of PI(4,5)P2 for maintaining the activity of the transient receptor potential canonical (TRPC)4beta. Pflugers Arch 465:1011–1021

    CAS  PubMed  Google Scholar 

  • Klein RM, Ufret-Vincenty CA, Hua L, Gordon SE (2008) Determinants of molecular specificity in phosphoinositide regulation. Phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is the endogenous lipid regulating TRPV1. J Biol Chem 283:26208–26216

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krauter T, Ruppersberg JP, Baukrowitz T (2001) Phospholipids as modulators of KATP channels: distinct mechanisms for control of sensitivity to sulphonylureas, K+ channel openers, and ATP. Mol Pharmacol 59:1086–1093

    CAS  PubMed  Google Scholar 

  • Kremeyer B et al (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66:671–680

    CAS  PubMed  Google Scholar 

  • Kruse M, Hammond GR, Hille B (2012) Regulation of voltage-gated potassium channels by PI(4,5)P2. J Gen Physiol 140:189–205

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kwon Y, Hofmann T, Montell C (2007) Integration of phosphoinositide- and calmodulin-mediated regulation of TRPC6. Mol Cell 25:491–503

    CAS  PubMed Central  PubMed  Google Scholar 

  • Langeslag M, Clark K, Moolenaar WH, van Leeuwen FN, Jalink K (2007) Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. J Biol Chem 282:232–239

    CAS  PubMed  Google Scholar 

  • Large WA, Saleh SN, Albert AP (2009) Role of phosphoinositol 4,5-bisphosphate and diacylglycerol in regulating native TRPC channel proteins in vascular smooth muscle. Cell Calcium 45:574–582

    CAS  PubMed  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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lemonnier L, Trebak M, Putney JW Jr (2008) Complex regulation of the TRPC3, 6 and 7 channel subfamily by diacylglycerol and phosphatidylinositol-4,5-bisphosphate. Cell Calcium 43:506–514

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li Y, Gamper N, Hilgemann DW, Shapiro MS (2005) Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci 25:9825–9835

    CAS  PubMed  Google Scholar 

  • Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–112

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin Z et al (2012) Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome. Am J Hum Genet 90:558–564

    CAS  PubMed Central  PubMed  Google Scholar 

  • Link TM, Park U, Vonakis BM, Raben DM, Soloski MJ, Caterina MJ (2010) TRPV2 has a pivotal role in macrophage particle binding and phagocytosis. Nat Immunol 11:232–239

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R (2007) The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54:905–918

    CAS  PubMed  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

    CAS  PubMed Central  PubMed  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

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Lopes CM, Zhang H, Rohacs T, Jin T, Yang J, Logothetis DE (2002) Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies. Neuron 34:933–944

    CAS  PubMed  Google Scholar 

  • Lukacs V, Thyagarajan B, Varnai P, Balla A, Balla T, Rohacs T (2007) Dual regulation of TRPV1 by phosphoinositides. J Neurosci 27:7070–7080

    CAS  PubMed  Google Scholar 

  • Lukacs V, Yudin Y, Hammond GR, Sharma E, Fukami K, Rohacs T (2013a) Distinctive changes in plasma membrane phosphoinositides underlie differential regulation of TRPV1 in nociceptive neurons. J Neurosci 33:11451–11463

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lukacs V, Rives JM, Sun X, Zakharian E, Rohacs T (2013b) Promiscuous activation of transient receptor potential vanilloid 1 channels by negatively charged intracellular lipids, the key role of endogenous phosphoinositides in maintaining channel activity. J Biol Chem 288:35003–35013

    CAS  PubMed  Google Scholar 

  • Ma R, Li WP, Rundle D, Kong J, Akbarali HI, Tsiokas L (2005) PKD2 functions as an epidermal growth factor-activated plasma membrane channel. Mol Cell Biol 25:8285–8298

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mercado J, Gordon-Shaag A, Zagotta WN, Gordon SE (2010) Ca2+-dependent desensitization of TRPV2 channels is mediated by hydrolysis of phosphatidylinositol 4,5-bisphosphate. J Neurosci 30:13338–13347

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miehe S, Bieberstein A, Arnould I, Ihdene O, Rutten H, Strubing C (2010) The phospholipid-binding protein SESTD1 is a novel regulator of the transient receptor potential channels TRPC4 and TRPC5. J Biol Chem 285:12426–12434

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mohapatra DP, Nau C (2005) Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. J Biol Chem 280:13424–13432

    CAS  PubMed  Google Scholar 

  • Montell C (2012) Drosophila visual transduction. Trends Neurosci 35:356–363

    CAS  PubMed Central  PubMed  Google Scholar 

  • Niemeyer BA, Bergs C, Wissenbach U, Flockerzi V, Trost C (2001) Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin. Proc Natl Acad Sci U S A 98:3600–3605

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Voets T (2013) The puzzle of TRPV4 channelopathies. EMBO Rep 14:152–163

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Mahieu F, Prenen J, Janssens A, Owsianik G, Vennekens R, Voets T (2006) The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate. EMBO J 25:467–478

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Owsianik G, Voets T (2008) Transient receptor potential channels meet phosphoinositides. EMBO J 27:2809–2816

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Appendino G, Owsianik G (2012) The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch 464:425–458

    CAS  PubMed  Google Scholar 

  • Okamura Y, Murata Y, Iwasaki H (2009) Voltage-sensing phosphatase: actions and potentials. J Physiol 587:513–520

    CAS  PubMed Central  PubMed  Google Scholar 

  • Otsuguro K, Tang J, Tang Y, Xiao R, Freichel M, Tsvilovskyy V, Ito S, Flockerzi V, Zhu MX, Zholos AV (2008) Isoform-specific inhibition of TRPC4 channel by phosphatidylinositol 4,5-bisphosphate. J Biol Chem 283:10026–10036

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park U, Vastani N, Guan Y, Raja SN, Koltzenburg M, Caterina MJ (2011) TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception. J Neurosci 31:11425–11436

    CAS  PubMed Central  PubMed  Google Scholar 

  • Patil MJ, Belugin S, Akopian AN (2011) Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses. J Neurosci Res 89:945–954

    CAS  PubMed Central  PubMed  Google Scholar 

  • Premkumar LS, Raisinghani M, Pingle SC, Long C, Pimentel F (2005) Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation. J Neurosci 25:11322–11329

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Putney JW, Tomita T (2011) Phospholipase C signaling and calcium influx. Adv Enzyme Regul 52:152–164

    Google Scholar 

  • Qin F (2007) Regulation of TRP ion channels by phosphatidylinositol-4,5-bisphosphate. Handb Exp Pharmacol 509–525

    Google Scholar 

  • Rohacs T (2007) Regulation of TRP channels by PIP2. Pflugers Arch 453:753–762

    CAS  PubMed  Google Scholar 

  • Rohacs T (2009) Phosphoinositide regulation of non-canonical transient receptor potential channels. Cell Calcium 45:554–565

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rohacs T (2013) Regulation of transient receptor potential channels by the phospholipase C pathway. Adv Biol Regul 53:341–355

    CAS  PubMed  Google Scholar 

  • Rohacs T, Nilius B (2007) Regulation of transient receptor potential (TRP) channels by phosphoinositides. Pflugers Arch 455:157–168

    CAS  PubMed  Google Scholar 

  • Rohacs T, Lopes C, Mirshahi T, Jin T, Zhang H, Logothetis DE (2002) Assaying phosphatidylinositol bisphosphate regulation of potassium channels. Methods Enzymol 345:71–92

    PubMed  Google Scholar 

  • Rohacs T, Lopes CM, Jin T, Ramdya PP, Molnar Z, Logothetis DE (2003) Specificity of activation by phosphoinositides determines lipid regulation of Kir channels. Proc Natl Acad Sci U S A 100:745–750

    CAS  PubMed Central  PubMed  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

    CAS  PubMed  Google Scholar 

  • Rosenhouse-Dantsker A, Logothetis DE (2007) Molecular characteristics of phosphoinositide binding. Pflugers Arch 455:45–53

    CAS  PubMed  Google Scholar 

  • Runnels LW, Yue L, Clapham DE (2002) The TRPM7 channel is inactivated by PIP2 hydrolysis. Nat Cell Biol 4:329–336

    CAS  PubMed  Google Scholar 

  • Saarikangas J, Zhao H, Lappalainen P (2010) Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides. Physiol Rev 90:259–289

    CAS  PubMed  Google Scholar 

  • Sachs F (2010) Stretch-activated ion channels: what are they? Physiology (Bethesda) 25:50–56

    CAS  Google Scholar 

  • Saleh SN, Albert AP, Large WA (2009a) Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP3 and PIP2 in rabbit coronary artery myocytes. J Physiol 587:5361–5375

    CAS  PubMed Central  PubMed  Google Scholar 

  • Saleh SN, Albert AP, Large WA (2009b) Obligatory role for phosphatidylinositol 4,5-bisphosphate in activation of native TRPC1 store-operated channels in vascular myocytes. J Physiol 587:531–540

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sarria I, Ling J, Zhu MX, Gu JG (2011) TRPM8 acute desensitization is mediated by calmodulin and requires PIP2: distinction from tachyphylaxis. J Neurophysiol 106:3056–3066

    CAS  PubMed Central  PubMed  Google Scholar 

  • Senning EN, Collins MD, Stratiievska A, Ufret-Vincenty CA, Gordon SE (2014) Regulation of TRPV1 by phosphoinositide (4,5)-bisphosphate: role of membrane asymmetry. J Biol Chem (in press)

    Google Scholar 

  • Shewan A, Eastburn DJ, Mostov K (2011) Phosphoinositides in cell architecture. Cold Spring Harb Perspect Biol 3:a004796

    PubMed Central  PubMed  Google Scholar 

  • Shi J, Ju M, Abramowitz J, Large WA, Birnbaumer L, Albert AP (2012) TRPC1 proteins confer PKC and phosphoinositol activation on native heteromeric TRPC1/C5 channels in vascular smooth muscle: comparative study of wild-type and TRPC1-/- mice. FASEB J 26:409–419

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shyng SL, Nichols CG (1998) Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282:1138–1141

    CAS  PubMed  Google Scholar 

  • Sowa NA, Street SE, Vihko P, Zylka MJ (2010) Prostatic acid phosphatase reduces thermal sensitivity and chronic pain sensitization by depleting phosphatidylinositol 4,5-bisphosphate. J Neurosci 30:10282–10293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stein AT, Ufret-Vincenty CA, Hua L, Santana LF, Gordon SE (2006) Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J Gen Physiol 128:509–522

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suh BC, Hille B (2002) Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis. Neuron 35:507–520

    CAS  PubMed  Google Scholar 

  • Suh BC, Hille B (2008) PIP2 is a necessary cofactor for ion channel function: how and why? Annu Rev Biophys 37:175–195

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suh BC, Inoue T, Meyer T, Hille B (2006) Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels. Science 314:1454–1457

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suh BC, Leal K, Hille B (2010) Modulation of high-voltage activated Ca2+ channels by membrane phosphatidylinositol 4,5-bisphosphate. Neuron 67:224–238

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sui JL, Petit-Jacques J, Logothetis DE (1998) Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates. Proc Natl Acad Sci U S A 95:1307–1312

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takezawa R, Schmitz C, Demeuse P, Scharenberg AM, Penner R, Fleig A (2004) Receptor-mediated regulation of the TRPM7 channel through its endogenous protein kinase domain. Proc Natl Acad Sci U S A 101:6009–6014

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thyagarajan B, Lukacs V, Rohacs T (2008) Hydrolysis of phosphatidylinositol 4,5-bisphosphate mediates calcium-induced inactivation of TRPV6 channels. J Biol Chem 283:14980–14987

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thyagarajan B, Benn BS, Christakos S, Rohacs T (2009) Phospholipase C-mediated regulation of transient receptor potential vanilloid 6 channels: implications in active intestinal Ca2+ transport. Mol Pharmacol 75:608–616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Toth B, Csanady L (2012) Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents. Proc Natl Acad Sci U S A 109:13440–13445

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trebak M, Lemonnier L, DeHaven WI, Wedel BJ, Bird GS, Putney JW Jr (2009) Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. Pflugers Arch 457:757–769

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE (2011) Localization of the PIP2 sensor of TRPV1 ion channels. J Biol Chem 286:9688–9698

    CAS  PubMed Central  PubMed  Google Scholar 

  • Varnai P, Thyagarajan B, Rohacs T, Balla T (2006) Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells. J Cell Biol 175:377–382

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walder RY, Landau D, Meyer P, Shalev H, Tsolia M, Borochowitz Z, Boettger MB, Beck GE, Englehardt RK, Carmi R, Sheffield VC (2002) Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet 31:171–174

    CAS  PubMed  Google Scholar 

  • Walder RY, Yang B, Stokes JB, Kirby PA, Cao X, Shi P, Searby CC, Husted RF, Sheffield VC (2009) Mice defective in Trpm6 show embryonic mortality and neural tube defects. Hum Mol Genet 18:4367–4375

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang YY, Chang RB, Waters HN, McKemy DD, Liman ER (2008) The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J Biol Chem 283:32691–32703

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Zhang X, Dong XP, Samie M, Li X, Cheng X, Goschka A, Shen D, Zhou Y, Harlow J, Zhu MX, Clapham DE, Ren D, Xu H (2012) TPC proteins are phosphoinositide-activated sodium-selective ion channels in endosomes and lysosomes. Cell 151:372–383

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weissgerber P, Kriebs U, Tsvilovskyy V, Olausson J, Kretz O, Stoerger C, Vennekens R, Wissenbach U, Middendorff R, Flockerzi V, Freichel M (2011) Male fertility depends on Ca2+ absorption by TRPV6 in epididymal epithelia. Sci Signal 4:ra27

    PubMed  Google Scholar 

  • Whorton MR, MacKinnon R (2011) Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium. Cell 147:199–208

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu LJ, Sweet TB, Clapham DE (2010) International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol Rev 62:381–404

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xie J, Sun B, Du J, Yang W, Chen HC, Overton JD, Runnels LW, Yue L (2011) Phosphatidylinositol 4,5-bisphosphate (PIP2) controls magnesium gatekeeper TRPM6 activity. Sci Rep 1:146

    PubMed Central  PubMed  Google Scholar 

  • Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T, Hara Y, Negoro T, Hiroi T, Kiuchi Y, Okada T, Kaneko S, Lange I, Fleig A, Penner R, Nishi M, Takeshima H, Mori Y (2008) TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14:738–747

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao J, Qin F (2009) Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor. PLoS Biol 7:e46

    PubMed  Google Scholar 

  • Yudin Y, Rohacs T (2011) Regulation of TRPM8 channel activity. Mol Cell Endocrinol 353:68–74

    PubMed Central  PubMed  Google Scholar 

  • Yudin Y, Lukacs V, Cao C, Rohacs T (2011) Decrease in phosphatidylinositol 4,5-bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels. J Physiol 589:6007–6027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T (2009) Inorganic polyphosphate modulates TRPM8 channels. PLoS One 4:e5404

    PubMed Central  PubMed  Google Scholar 

  • Zakharian E, Cao C, Rohacs T (2010) Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers. J Neurosci 30:12526–12534

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zakharian E, Cao C, Rohacs T (2011) Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5)P2. FASEB J 25:3915–3928

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang H, Craciun LC, Mirshahi T, Rohacs T, Lopes CM, Jin T, Logothetis DE (2003) PIP2 activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. Neuron 37:963–975

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Zhang X, Li X, Xu H (2012a) Phosphoinositide isoforms determine compartment-specific ion channel activity. Proc Natl Acad Sci U S A 109:11384–11389

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang X, Mak S, Li L, Parra A, Denlinger B, Belmonte C, McNaughton PA (2012b) Direct inhibition of the cold-activated TRPM8 ion channel by Galpha(q). Nat Cell Biol 14:851–858

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rutgers – New Jersey Medical School, Newark, NJ, USA

    Tibor Rohacs

Authors
  1. Tibor Rohacs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tibor Rohacs .

Editor information

Editors and Affiliations

  1. Laboratory Ion Channel Research, Campus Gasthuisberg, KU Leuven Department, Cell Mol Medicin, Leuven, Belgium

    Bernd Nilius

  2. Pharmakologie und Toxikologie, Universität des Saarlandes, Institut für Experimentelle u. Klinische, Homburg, Germany

    Veit Flockerzi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Rohacs, T. (2014). Phosphoinositide Regulation of TRP Channels. In: Nilius, B., Flockerzi, V. (eds) Mammalian Transient Receptor Potential (TRP) Cation Channels. Handbook of Experimental Pharmacology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-05161-1_18

Download citation

Publish with us

Policies and ethics

Search

Navigation