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TRPV4, a Regulatory Channel in the Production of Cerebrospinal Fluid by the Choroid Plexus

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Role of the Choroid Plexus in Health and Disease

Part of the book series: Physiology in Health and Disease ((PIHD))

Abstract

Transient receptor potential, vanilloid 4 (TRPV4) channel is an osmo- and mechano-sensitive nonselective cation channel expressed throughout the body. TRPV4 is activated and regulated by a wide variety of endogenous and exogenous stimuli. In addition to its relatively ubiquitous distribution and regulation by diverse stimuli including pressure, pH, inflammation, cell swelling and cytokines, TRPV4 appears to be a hub protein in many signaling cascades integrating input from multiple receptors and kinases. TRPV4 is present in the apical membrane of choroid plexus epithelial cells and emerging studies have linked this channel with changes in transepithelial ion and water flux.

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References

  • Akiyama T, Ivanov M, Nagamine M et al (2016) Involvement of TRPV4 in serotonin-evoked scratching. J Invest Dermatol 136(1):154–160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alenmyr L, Uller L, Greiff L, Hogestatt ED, Zygmunt PM (2014) TRPV4-mediated calcium influx and ciliary activity in human native airway epithelial cells. Basic Clin Pharmacol Toxicol 114(2):210–216

    Article  PubMed  CAS  Google Scholar 

  • Alessandri-Haber N, Yeh JJ, Boyd AE, Parada CA et al (2003) Hypotonicity induces TRPV4-mediated nociception in rat. Neuron 39(3):497–511

    Article  PubMed  CAS  Google Scholar 

  • Alessandri-Haber N, Dina OA, Joseph EK, Reichling D, Levine JD (2006) A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is engaged by concerted action of inflammatory mediators. J Neurosci 26(14):3864–3874

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alessandri-Haber N, Dina OA, Joseph EK, Reichling D, Levine JD (2008) Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia. J Neurosci 28(5):1046–1057

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alessandri-Haber N, Dina OA, Chen X, Levine JD (2009) TRPC1 and TRPC6 channels cooperate with TRPV4 to mediate mechanical hyperalgesia and nociceptor sensitization. J Neurosci 29:6217–6228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alvarez DF, King JA, Weber D, Addison E, Liedtke W, Townsley MI (2006) Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury. Circ Res 99:988–995

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arniges M, Fernandez-Fernandez JM, Albrecht N, Shaefer M, Valverde MA (2006) Human TRPV4 channel splice variants revealed a key role of ankyrin domains in multimerization and trafficking. J Biol Chem 281(3):1580–1586

    Article  PubMed  CAS  Google Scholar 

  • Bagher P, Beleznai T, Kansui Y, Mitchell R, Garland CJ, Dora KA (2012) Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca2 events, and IKCa channels, reducing arteriolar tone. Proc Natl Acad Sci U S A 109:18174–18179

    Article  PubMed  PubMed Central  Google Scholar 

  • Bai JZ, Lipski J (2010) Differential expression of TRPM2 and TRPV4 channels and their potential role in oxidative stress-induced cell death in organotypic hippocampal culture. Neurotoxicology 31:204–214

    Article  PubMed  CAS  Google Scholar 

  • Becker D, Muller M, Leuner K, Jendrach M (2008) The C-terminal domain of TRPV4 is essential for plasma membrane localization. Mol Membr Biol 25(2):139–151

    Article  PubMed  CAS  Google Scholar 

  • Benfenati V, Amiry-Moghaddam M, Caprini M, Mylonakou MN et al (2007) Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience 148(4):876–892

    Article  PubMed  CAS  Google Scholar 

  • Benfenati V, Caprini M, Dovizio M, Mylonakou MN et al (2011) An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proc Natl Acad Sci U S A 108(6):2563–2568

    Article  PubMed  PubMed Central  Google Scholar 

  • Brohawn SG, Su Z, MacKinnon R (2014) Mechanosensitivity is mediated directly by the lipid membrane in TRAAK and TREK1 K channels. Proc Natl Acad Sci U S A 111:3614–3619

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cao DS, Yu SQ, Premkumar LS (2009) Modulation of transient receptor potential Vanilloid 4-mediated membrane currents and synaptic transmission by protein kinase C. Mol Pain 5:5

    PubMed  PubMed Central  Google Scholar 

  • Cao DS, Anishkin A, Zinkevich NS, Nishijima Y et al (2018) Transient receptor potential vanilloid 4 (TRPV4) activation by arachnidonic acid requires protein kindase A-mediated phosphorylation. J Biol Chem 293(14):5307–5322

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen X, Alessandri-Haber N, Levine JD (2007) Marked attenuation of inflammatory mediator-induced C-fiber sensitization for mechanical and hypotonic stimuli in TRPV4−/−mice. Mol Pain 3:31

    PubMed  PubMed Central  Google Scholar 

  • Cheng X, Shen D, Samie M, Xu H (2011) Mucolipins: intracellular TRPML1-3 channels. FEBS Lett 584(10):2013–2021

    Article  CAS  Google Scholar 

  • Corrigan MA, Johnson GP, Stavenschi E, Riffault M, Labour MN, Hoey DA (2018) TRPV4-mediates oscillatory fluid shear mechanotransduction in mesenchymal stem cells in part via the primary cilium. Sci Rep 8(1):3824

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cortright DN, Szallasi A (2009) TRP channels and pain. Curr Pharm Des 15:1736–1749

    Article  PubMed  CAS  Google Scholar 

  • Cosens DJ, Manning A (1969) Abnormal electroretinogram from a Drosophila mutant. Nature 224(5216):285–287

    Article  PubMed  CAS  Google Scholar 

  • Cuajungco MP, Grimm C, Oshima K, D’hoedt D et al (2006) PACSINs bind to the TRPV4 cation channel. J Biol Chem 281:18753–18762

    Article  PubMed  CAS  Google Scholar 

  • D’Aldebert E, Cenac N, Rousset P et al (2011) Transient receptor potential vanilloid 4 activated inflammatory signals by intestinal epithelial cells and colitis in mice. Gastroenterology 140:275–285

    Article  PubMed  CAS  Google Scholar 

  • Darby WG, Potocnik S, Ramachandran R, Hollenberg MD, Woodman OL, McIntyre P (2018) Shear stress sensitizes TRPV4 in endothelium-dependent vasodilation. Pharmacol Res 133:152–159

    Article  PubMed  CAS  Google Scholar 

  • Dejana E, Orsenigo F (2013) Endothelial adherens junctions at a glance. J Cell Sci 126:2545–2549

    Article  PubMed  CAS  Google Scholar 

  • Delery EC, MacLean AG (2019) Culture model for non-human primate choroid plexus. Front Cell Neuro 13:296

    Google Scholar 

  • Deng Z, Paknejad D, Maksaev G et al (2018) Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. Nat Struct Mol Biol 25(3):252–260

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Deruyver Y, Weyne E, Dewulf K et al (2018) Intravesical activation of the cation channel TRPV4 improves bladder function in a rat model for detrusor underactivity. Eru Urol 74(3):336–345

    Article  Google Scholar 

  • D’hoedt D, Owsianik G, Prenen J, Cuajungco MP et al (2007) Stimulus-specific modulation of the cation channel TRPV4 by PACSIN-3. J Biol Chem 283:6272–6280

    Article  CAS  Google Scholar 

  • Du J, Ma X, Shen B, Huang Y, Birnbaumer L, Yao X (2014) TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel. FASEB J 28(11):4677–4685

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dubowitz V, Daniels RJ, Davies KE (1995) Olivopontocerebellar hypoplasia with anterior horn cell involvement (SMA) does not localize to chromosome 5q. Neuromuscul Disord 5(1):25–29

    Article  PubMed  CAS  Google Scholar 

  • Dunn KM, Hill-Eubanks DC, Liedtke WB, Nelson MT (2013) TRPV4 channels stimulate Ca2+-induced Ca2+ release in astrocytic endfeet and amplify neurovascular coupling responses. Proc Natl Acad Sci U S A 110(15):6157–6162

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Everaerts W, Nilius B, Owsianik G (2010) The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog Biophys Mol Biol 103:2–17

    Article  PubMed  CAS  Google Scholar 

  • Fan HC, Zhang X, McNaughton PA (2009) Activation of the TRPV4 ion channel is enhanced by phosphorylation. J Biol Chem 284(41):27884–27891

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fernandes J, Lornezo IM, Andrade YN, Garcia-Elias A et al (2008) IP3 sensitizes TRPV4 channel to the mechano- and osmotransducing messenger 5′,6′ epoxyeicosatrienoic acid. J Cell Biol 181:143–155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ferrandiz-Hertas C, Mathivanan S, Jakob Wolf C, Devesa I, Ferrer-Montiel A (2014) Trafficking of ThermoTRP channels. Membranes (Basel) 4(3):525–564

    Article  CAS  Google Scholar 

  • Fichna J, Mokrowiecka A, Cygankiewicz AI, Zakrzewski PK et al (2012) Transient receptor potential vanilloid 4 blockade protects against experimental colitis in mice: a new strategy for inflammatory bowel diseases treatment? Neurogastroenterol Motil 24:e557–e560

    Article  PubMed  CAS  Google Scholar 

  • Fu Y, Subramanya A, Rozansky D, Cohen DM (2006) WNK kinases influence TRPV4 channel function and localization. Am J Physiol Ren Physiol 290:F1305–F1314

    Article  CAS  Google Scholar 

  • Gao X, Wu L, O’Neil RG (2003) Temperature-modulated diversity of TRPV4 channel gating: activation by physical stresses and phorbol ester derivatives through protein kinase C-dependent and -independent pathways. J Biol Chem 278:27129–27137

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Elias A, Lorenzo IM, Vicente R, Valverde MA (2008) IP3 receptor binds to and sensitizes TRPV4 channel to osmotic stimuli via a calmodulin site. J Biol Chem 283:31284–31288

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Elias A, Mrkonjic S, Pardo-Pastor C, Inada H et al (2013) Phosphatidylinositol-4,5-biphosphate-dependent rearrangement of TRPV4 cytosolic tails enables channel activation by physiological stimuli. Proc Natl Acad Sci USA 110:9553–9558

    Article  PubMed  PubMed Central  Google Scholar 

  • Gavaert T, Vriens J, Segal A, Everaerts W et al (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117(11):3453–3462

    Article  CAS  Google Scholar 

  • Gees M, Colsoul B, Nilius B (2010) The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol 2(10):a003962

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Goswami C, Kuhn J, Heppenstall PA, Hucho T (2010) Importance of non-selective cation channel TRPV4 interaction with cytoskeleton and their reciprocal regulations in cultured cells. PLoSOne 5:e11654

    Article  CAS  Google Scholar 

  • Grant AD, Cottrell GS, Amadesi S, Trevisani M et al (2007) Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 157(3):715–733

    Article  CAS  Google Scholar 

  • Gregoridades JMC, Madaris A, Alvarez F, Alvarez-Leefmans FJ (2019) Genetic and pharmacological inactivation of apical Na+-K+2Cl- cotransporter 1 in choroid plexus epithelial cells reveals the physiological function of the cotransporter. Am J Physiol Cell Physiol 316:C525–C544

    Article  Google Scholar 

  • Güler A, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M (2002) Heat-evoked activation of TRPV4 (VR-OAC). J Neurosci 22:6408–6414

    Article  PubMed  PubMed Central  Google Scholar 

  • Hatano N, Suzuki H, Itoh Y, Muraki K (2013) TRPV4 partially participates in proliferation of human brain capillary endothelial cells. Life Sci 92:317–324

    Article  PubMed  CAS  Google Scholar 

  • Hochstetler AE, Whitehouse L, Antonellis P, Berbari NF, Blazer-Yost B (2018) Characterizing the expression of TRPV4 in the choroid plexus epithelia as a prospective component in the development of hydrocephalus in the Gas8GT juvenile mutant mouse. FASEB J 32:750.12

    Google Scholar 

  • Inda H, Procko E, Sotomayor M, Gaudet R (2012) Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel. Biochemistry 51:6195–6206

    Article  CAS  Google Scholar 

  • Jang Y, Jung J, Kim H, Oh J et al (2012) Axonal neuropathy-associated TRPV4 regulates neurotrophic factor-derived axonal growth. J Biol Chem 287:6014–6024

    Article  PubMed  CAS  Google Scholar 

  • Janssen DA, Hoenderop JG, Jansen KC, Kemp AW, Heesakkers JP, Schalken JA (2011) The mechanoreceptor TRPV4 is localized in adherence junctions of the human bladder urothelium: a morphological study. J Urol 186:1121–1127

    Article  PubMed  CAS  Google Scholar 

  • Jie P, Lu Z, Hong Z, Li L et al (2016) Activation of transient receptor potential vanilloid 4 is involved in neuronal injury in middle cerebral artery occlusion in mice. Mol Neurobiol 53:8–17

    Article  PubMed  CAS  Google Scholar 

  • Klas J, Wolburg H, Terasaki T, Fricker G, Reichel V (2010) Characterization of immortalized choroid plexus epithelial cell lines for studies of transport processes across the blood-cerebrospinal fluid barrier. Cerebrosp Fluid Res 7:11

    Article  CAS  Google Scholar 

  • Köhler R, Heyken WT, Heinau P, Schubert R et al (2006) Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation. Arterioscler Thromb Vasc Biol 26:1495–1502

    Article  CAS  PubMed  Google Scholar 

  • Kornak U, Mundlos S (2003) Genetic disorders of the skeleton: a developmental approach. Am J Hum Genet 73:447–474

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kumar H, Lee SH, Kim KT, Zeng X, Han I (2018) TRPV4: a sensor for homeostasis and pathologcial events in the CNS. Mol Neurobiol 55:8695–8708

    Article  PubMed  CAS  Google Scholar 

  • Kung C (2005) A possible unifying principle for mechanosensation. Nature 436:647–654

    Article  PubMed  CAS  Google Scholar 

  • Lamande SR, Yuan Y, Gresshoff IL, Rowley L et al (2011) Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Nat Genet 43:1142–1146

    Article  PubMed  CAS  Google Scholar 

  • Lanciotti A, Brignone MS, Molinari P, Visentin S et al (2012) Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum Mol Genet 21:2166–2180

    Article  PubMed  CAS  Google Scholar 

  • Lee JC, Choe SY (2014) Age-related changes in the distribution of transient receptor potential vanilloid 4 channel (TRPV4) in the central nervous system of rats. J Mol Histol 45(5):497–505

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Iida T, Mizuno A, Suzuki M, Caterina MJ (2005) Altered thermal selection behavior in mice lacking transient receptor potential vanilloid 4. J Neurosci 25(5):1304–1310

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee EJ, Shin SH, Chun J, Hyun S, Kim Y, Kang SS (2010) The modulation of TRPV4 channel activity through its Ser 824 residue phosphorylation by SGK1. Anim Cell Sys 14(2):99–114

    Article  CAS  Google Scholar 

  • Lee JC, Joo KM, Choe SY, Cha CI (2012) Region-specific changes in the immunoreactivity of TRPV4 expression in the central nervous system of SOD1 (G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis. J Mol Histol 43(6):625–631

    Article  PubMed  CAS  Google Scholar 

  • Lei L, Cao X, Yang F et al (2013) A TRPV4 channel C-terminal folding recognition domain critical for trafficking and function. J Biol Chem 288:10427–10439

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li J, Kanju P, Patterson M, Chew WL et al (2011) TRPV4-mediated calcium influx into bronchial epithelia upon exposure to diesel exhaust particles. Eviron Health Perspect 119(6):784–793

    Article  CAS  Google Scholar 

  • Li L, Qu W, Zhou L, Lu Z et al (2013) Activation of transient receptor potential vanilloid 4 increases NMDA-activated current in hippocampal pyramidal neurons. Front Cell Neurosci 7:17

    PubMed  PubMed Central  CAS  Google Scholar 

  • Li M, Fang XZ, Zheng YF et al (2019) Transient receptor potential Vanilloid 4 is a critical mediator in LPS mediated inflammation by mediating calcineurin/NFATc3 signaling. Biochem Biophys Res Commun 513(4):1005–1012

    Article  PubMed  CAS  Google Scholar 

  • Liedtke W (2008) Molecular mechanisms of TRPV4-mediated neural signaling. Ann N Y Acad Sci 1144:42–52

    Article  PubMed  CAS  Google Scholar 

  • Liedtke W, Friedman JM (2003) Abnormal osmotic regulation in trpv4−/− mice. Proc Natl Acad Sci USA 100(23):13698–13703

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Liedtke W, Choe Y, Marti-Renom MA, Bell AM et al (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103(3):525–535

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu X, Bandyopadhyay BC, Nakamoto T, Singh B et al (2006) A role for AQP5 in activation of TRPV4 by hypotonicity: concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery. J Biol Chem 281:15485–15495

    Article  PubMed  CAS  Google Scholar 

  • Loot AE, Popp R, Fisslthaler B, Vriens J, Nilius B, Fleming I (2008) Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation. Cardiovasc Res 80:445–452

    Article  CAS  PubMed  Google Scholar 

  • Luo N, Conwell MD, Chen X et al (2014) Primary cilia signaling mediates intraocular pressure sensation. Proc Natl Acad Sci U S A 111(35):12871–12876

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma X, Cao J, Luo J, Nilius B et al (2010) Depletion of intracellular Ca2+ stores stimulates the translocation of vanilloid transient receptor potential 4-c1 heteromeric channels to the plasma membrane. Arterioscler Thromb Vasc Biol 30:2249–2255

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ma X, Cheng KT, Wong CO, O’Neil RG et al (2011) Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. Cell Calcium 50(6):502–509

    Article  PubMed  CAS  Google Scholar 

  • Main M, Kairon H, Mercuri E, Muntoni F (2003) The Hammersmith functional motor scale for children with spinal muscular atrophy: a scale to test ability and monitor progress in children with limited ambulation. Eur J Paediatr Neurol 7:155–159

    Article  PubMed  Google Scholar 

  • Mamenko M, Zaika OL, Boukelmoune N, Berrout J, O’Neil RG, Pochynyuk O (2013) Discrete control of TRPV4 channel function in the distal nephron by protein kinases A and C. J Biol Chem 288:20306–20314

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Marrelli SP, O’Neil RG, Brown RC, Bryan RM Jr (2007) PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries. Am J Physiol Heart Circ Physiol 292:H1390–H1397

    Article  PubMed  CAS  Google Scholar 

  • Masuyama R, Vriens J, Voets T, Karashima Y et al (2008) TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts. Cell Metab 8:257–265

    Article  PubMed  CAS  Google Scholar 

  • Masuyama R, Mizuno A, Komori H, Kajiya H et al (2012) Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass. J Bone Miner Res 27:1708–1721

    Article  PubMed  CAS  Google Scholar 

  • McEntagart M (2012) TRPV4 axonal neuropathy spectrum disorder. J Clin Neurosci 19:927–933

    Article  PubMed  Google Scholar 

  • Mendoza SA, Fang J, Gutterman DD, Wilcox DA et al (2010) TRPV4-mediated endothelial Ca2 influx and vasodilation in response to shear stress. Am J Physiol Heart Circ Physiol 298:H466–H476

    Article  PubMed  CAS  Google Scholar 

  • Millar ID, Bruce Jl, Brown PD (2007) Ion channel diversity, channel expression, and function in the choroid plexuses. Cerebrospinal Fluid Res 4:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Narita K, Sasamoto S, Koizumi S, Okazaki S et al (2015) TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport. FASEB J 29(6):2247–2259

    Article  PubMed  CAS  Google Scholar 

  • Nilius B, Honore E (2012) Sensing pressure with ion channels. Trends Neurosci 35:477–486

    Article  PubMed  CAS  Google Scholar 

  • Nishimura G, Dai J, Lausch E, Unger S et al (2010) Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morpquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. Am J Med Genet 152A:1443–1449

    Article  PubMed  CAS  Google Scholar 

  • Owsianik G, Cao L, Nilius B (2003) Rescue of functional DeltaF508-CFTR channels by co-expression with truncated CFTR constructs in COS-1 cells. FEBS Lett 554:173–178

    Article  PubMed  CAS  Google Scholar 

  • Pairet N, Mang S, Fois G, Keck M et al (2018) TRPV4 inhibition attenuates stretch-induced inflammatory cellular responses and lung barrier dysfunction during mechanical ventilation. PLoS One 13:e0196055

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pankey EA, Zsombok A, Lasker GF, Kadowitz PJ (2014) Analysis of responses to the TRPV4 agonist GSK1016790A in the pulmonary vascular bed of the intact-chest rat. Am J Physiol Heart Circ Physiol 306(1):H33–H40

    Article  PubMed  CAS  Google Scholar 

  • Pedersen SF, Nilius B (2007) Transient receptor potential channels in mechanosensing and cell volume regulation. Methods Enzymol 428:183–207

    Article  PubMed  CAS  Google Scholar 

  • Poole DP, Amadesi S, Veldhuis NA, Abogadie FC et al (2013) Protease-activated receptor 2 (PAR2) protein and transient receptor potential vanilloid 4 (TRPV4) protein coupling is required for sustained inflammatory signaling. J Biol Chem 288(8):5790–5802

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Preston D, Simpson S, Halm D, Hochstetler A et al (2018) Activation of TRPV4 stimulates transepithelial ion flux in a porcine choroid plexus cell line. Am J Physiol Cell Physiol 315(3):C357–C366

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pries AR, Secomb TW (2014) Making microvascular networks work: angiogenesis, remodeling, and pruning. Physiology 29:446–455

    Article  PubMed  PubMed Central  Google Scholar 

  • Rahman M, Sun R, Mukherjee S, Nilius B, Janssen LJ (2018) TRPV4 stimulation releases ATP via Pannexin channels in human pulmonary fibroblasts. Am J Respir Cell Mol Biol 59(1):87–95

    Article  PubMed  CAS  Google Scholar 

  • Ryskamp DA, Jo AO, Frye AM, Vazquez-Chona F et al (2014) Swelling and eicosanoid metabolites differentially gate TRPV4 channels in retinal neurons and glia. J Neurosci 34:15689–15700

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saigusa T, Yue Q, Bunni MA, Bell PD, Eaton DC (2019) Loss of primary cilia increase polycystin-2 and TRPV4 and the appearance of a nonselective cation channel in the mouse cortical collecting duct. Am J Physiol Renal Physiol 317(3):F632–F637

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Saliez J, Bouzin C, Rath G, Ghisdal P et al (2008) Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells. Circulation 117:1065–1074

    Article  PubMed  CAS  Google Scholar 

  • Schierling W, Troidi K, Apfelbeck H, Troidi C et al (2011) Cerebral arteriogenesis is enhanced by pharmacological as well as fluid-sheer-stress activation of the TRPV4 calcium channel. Eur J Vasc Endovasc Surg 41:589–596

    Article  PubMed  CAS  Google Scholar 

  • Schroten M, Hanisch F, Quednau N, Stump C et al (2012) A novel porcine in vitro model of the blood-cerebrospinal fluid barrier with strong barrier function. PloS ONE 7:e39835

    Google Scholar 

  • Schwerk C, Papandreou T, Schuhmann D, Nickol L et al (2012) Polar invasion and translocation of Neisseria meningitides and Streptococcus suis in a novel human model of the blood-cerebrospinal fluid barrier. Plos ONE 7:e30069

    Google Scholar 

  • Shavit-Stein E, Artan-Furman A, Feingold E, Ben Shimon M et al (2017) Protease activated receptor 2 (PAR2) induces long-term depression in the hippocampus through transient receptor potential vanilloid 4 (TRPV4). Front Mol Neurosci 10:42

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shi M, Du F, Liu Y, Li L et al (2013) Glial cell-expressed mechanosensitive channel TRPV4 mediates infrasound-induced neuronal impairment. Acta Neuropathol 126:725–739

    Article  PubMed  CAS  Google Scholar 

  • Shibasaki K, Tominaga M (2007) Implication that TRPV4 activation induces the excitation of astrocytes. In: Proceedings of annual meeting of the Physiological Society of Japan, pp 082–082

    Google Scholar 

  • Shibasaki K, Ikenaka K, Tamalu F, Tominaga M, Ishizaki Y (2014) A novel subtype of astrocytes expressing TRPV4 (transient receptor potential vanilloid 4) regulates neuronal excitability via release of gliotransmitters. J Biol Chem 289(21):14470–14480

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shikano M, Ueda T, Kamiya T, Ishida Y et al (2011) Acid inhibits TRPV4 mediated Ca2+ influx in mouse esophageal epithelial cells. Neurogastroenterol Motil 23:1020–1028

    Article  PubMed  CAS  Google Scholar 

  • Shin SH, Lee EJ, Hyun S, Chun J, Kim Y, Kang SS (2012) Phosphorylation on the Ser 824 residue of TRPV4 prefers to bind with F-actin than with microtubulues to expand the cell surface area. Cell Signal 24(3):641–651

    Article  PubMed  CAS  Google Scholar 

  • Simpson S, Preston D, Schwerk C, Schroten H, Blazer-Yost B (2019) Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells. Am J Physiol Cell Physiol 317(5):C881–C893. Ahead of print

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Smith H, Hochstetler A, Preston D, Balzer-Yost BL (2019) Preclinical testing of TRPV4 antagonists for the treatment of hydrocephalus. FASEB J 33:A708.4

    Article  Google Scholar 

  • Sonkusare SK, Bonev AD, Ledoux J et al (2012) Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science 336(6081):597–601

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stewart AP, Smith GD, Sandford RN, Edwardson JM (2010) Atomic force microscopy reveals the alternating subunit arrangement of the TRPP2-TRPV4 heterotetramer. Biophys J 99(3):790–797

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Strotmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD (2000) OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nat Cell Biol 2:695–702

    Article  PubMed  CAS  Google Scholar 

  • Strotmann R, Schultz G, Plant TD (2003) Ca2+-dependent potentiation of the nonselective cation channel TRPV4 is mediated by a C-terminal calmodulin binding site. J Biol Chem 278:26541–26549

    Article  PubMed  CAS  Google Scholar 

  • Suzuki M, Mizuno A, Kodaira K, Imai M (2003) Impaired pressure sensation with mice lacking TRPV4. J Biol Chem 278:22664–22668

    Article  PubMed  CAS  Google Scholar 

  • Tabuchi K, Suzuki M, Mizuno A, Hara A (2005) Hearing impairment in TRPV4 knockout mice. Neurosci Lett 382:304–308

    Article  PubMed  CAS  Google Scholar 

  • Takayama Y, Shibasaki K, Suzuki Y, Yamanaka A, Tominaga M (2014) Modulation of water efflux through functional interaction between TRPV4 and TMEM16A/anoctamin 1. FASEB J 28(5):2238–2248

    Article  PubMed  CAS  Google Scholar 

  • Teng J, Loukin SH, Anishkin A, Kung C (2015) L596-W733 bond between the start of the S4-S5 linker and the TRP box stabilizes the closed state of the TRPV4 channel. Proc Natl Acad Sci USA 112(11):3386–3391

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Thorneloe KS, Cheung M, Bao W, Alsaid H et al (2012) An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med 4:159ra148

    Article  PubMed  CAS  Google Scholar 

  • Verma P, Kumar A, Goswami C (2010) TRPV4-mediated channelopathies. Channels 4(4):319–328

    Article  PubMed  CAS  Google Scholar 

  • Villalta PC, Rocic P, Townsley MI (2014) Role of MMP2 and MMP9 in TRPV4-induced lunginjury. Am J Physiol Lung Cell Mol Physiol 307:L652–L659

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vriens J, Owsianik G, Fisslthalter B, Suzuki M et al (2005) Modulation of the Ca2+ permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ Res 97:908–915

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Fu X, Gaiser S, Kottgen M et al (2007) OS-9 regulates the transit and polyubiquitination of TRPV4 in the endoplasmic reticulum. J Biol Chem 282:36561–36570

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Zhou L, An D, Xu W et al (2019) TRPV4-induced inflammatory response is involved in neuronal death in pilocarpine model of temporal lobe epilepsy in mice. Cell Death Dis 10:386

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B (2002) Heat-evoked activation of TRPV4 channels in an HEK293 cell expression system and in native mouse aorta endothelial cells. J Biol Chem 277:47044–47051

    Article  PubMed  CAS  Google Scholar 

  • Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nilius B (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–438

    Article  PubMed  CAS  Google Scholar 

  • Wegierski T, Hill K, Schaefer M, Walz G (2006) The HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels. EMBO J 25:5659–5669

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wegierski T, Lewandrowski U, Muller B, Sickmann A, Walz G (2009) Tyrosine phosphorylation modulates the activity of TRPV4 in response to defined stimuli. J Biol Chem 284:2923–2933

    Article  PubMed  CAS  Google Scholar 

  • White JPM, Cibelli M, Urban L, Nilius B, McGeown JG, Nagy I (2016) TRPV4: molecular conductor of a diverse orchestra. Physiol Rev 96(3):911–973

    Article  PubMed  CAS  Google Scholar 

  • Willette R, Bao W, Nerurkar S, Yue TL et al (2007) Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: part 2. J Pharmacol 326(2):443–452

    Google Scholar 

  • Wu HM, Huang Q, Yuan Y, Granger HJ (1996) VEGF induces NO-dependent hyperpermeability in coronary venules. Am J Physiol Heart Circ Physiol 271:H2735–H2739

    Article  CAS  Google Scholar 

  • Wu S, Jian MY, Xu YC, Zhou C et al (2009) Ca2 entry via alpha1G and TRPV4 channels differentially regulates surface expression of P-selectin and barrier integrity in pulmonary capillary endothelium. Am J Physiol Lung Cell Mol Physiol 297:L650–L657

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xia Y, Fu Z, Hu J, Huang C et al (2013) TRPV4 channel contributes to serotonin-induced pulmonary vasoconstriction and the enhanced vascular reactivity in chronic hypoxia pulmonary hypertension. Am J Physiol Cell Physiol 305(7):C704–C715

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yu FJ, Yarov-Yarovoy V, Gutman GA, Catterall WA (2005) Overview of molecular relationship in the voltage-gated ion channel superfamily. Pharmacol Rev 57:387–395

    Article  PubMed  CAS  Google Scholar 

  • Zerangue N, Schwappach B, Jan YN, Jan LY (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22(3):537–548

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Wang YH, Ge HY, Arendt-Nielsen L, Wang R, Yue SW (2008) A transient receptor potential vanilloid 4 contributes to mechanical allodynia following chronic compression of dorsal root ganglion in rats. Neurosci Lett 432(3):222–227

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors are supported by grants from the United States Department of Defense, Investigator Initiated Research Award W81XWH-16-PRMRP-IIRA and the Mayfield Education and Research Foundation.

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Authors and Affiliations

  1. Department of Biology, Indiana University, Purdue University, Indianapolis, IN, USA

    Alexandra E. Hochstetler, Makenna M. Reed & Bonnie L. Blazer-Yost

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  1. Alexandra E. Hochstetler
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  2. Makenna M. Reed
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  3. Bonnie L. Blazer-Yost
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Correspondence to Bonnie L. Blazer-Yost .

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  1. Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Jeppe Praetorius

  2. Department of Biology, Indiana University – Purdue University Indianapolis, Indianapolis, IN, USA

    Bonnie Blazer-Yost

  3. Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Helle Damkier

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Hochstetler, A.E., Reed, M.M., Blazer-Yost, B.L. (2020). TRPV4, a Regulatory Channel in the Production of Cerebrospinal Fluid by the Choroid Plexus. In: Praetorius, J., Blazer-Yost, B., Damkier, H. (eds) Role of the Choroid Plexus in Health and Disease. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-0716-0536-3_7

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