Skip to main content

Advertisement

Log in

Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells

  • Original Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Mechanosensitive ion channels are implicated in the biology of touch, pain, hearing and vascular reactivity; however, the identity of these ion channels and the molecular basis of their activation is poorly understood. We previously found that transient receptor potential vanilloid 4 (TRPV4) is a receptor operated ion channel that is sensitised and activated by mechanical stress. Here, we investigated the effects of mechanical stimulation on TRPV4 localisation and activation in native and recombinant TRPV4-expressing cells. We used a combination of total internal reflection fluorescence microscopy, cell surface biotinylation assay and Ca2+ imaging with laser scanning confocal microscope to show that TRPV4 is expressed in primary vascular endothelial cells and that shear stress sensitises the response of TRPV4 to its agonist, GSK1016790A. The sensitisation was attributed to the recruitment of intracellular pools of TRPV4 to the plasma membrane, through the clathrin and dynamin-mediated exocytosis. The translocation was dependent on ILK/Akt signalling pathway, release of Ca2+ from intracellular stores and we demonstrated that shear stress stimulated phosphorylation of TRPV4 at tyrosine Y110. Our findings implicate calcium-sensitive TRPV4 translocation in the regulation of endothelial responses to mechanical stimulation.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Delmas P, Hao J, Rodat-Despoix L (2011) Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat Rev Neurosci 12(3):139–153. doi:10.1038/nrn2993

    Article  PubMed  CAS  Google Scholar 

  2. Yashiro K, Shiratori H, Hamada H (2007) Haemodynamics determined by a genetic programme govern asymmetric development of the aortic arch. Nature 450(7167):285–288. doi:10.1038/nature06254

    Article  PubMed  CAS  Google Scholar 

  3. Ranade SS, Qiu Z, Woo S-H, Hur SS, Murthy SE, Cahalan SM, Xu J, Mathur J, Bandell M, Coste B, Li Y-SJ, Chien S, Patapoutian A (2014) Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci USA 111(28):10347–10352. doi:10.1073/pnas.1409233111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Orr AW, Helmke BP, Blackman BR, Schwartz MA (2006) Mechanisms of mechanotransduction. Dev Cell 10(1):11–20. doi:10.1016/j.devcel.2005.12.006

    Article  PubMed  CAS  Google Scholar 

  5. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10(1):53–62. doi:10.1038/nrm2596

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Huang S, Ingber DE (2005) Cell tension, matrix mechanics, and cancer development. Cancer Cell 8(3):175–176. doi:10.1016/j.ccr.2005.08.009

    Article  PubMed  CAS  Google Scholar 

  7. Lansman JB, Franco-Obregon A (2006) Mechanosensitive ion channels in skeletal muscle: a link in the membrane pathology of muscular dystrophy. Clin Exp Pharmacol Physiol 33(7):649–656. doi:10.1111/j.1440-1681.2006.04393.x

    Article  PubMed  CAS  Google Scholar 

  8. Discher DE, Janmey P, Wang YL (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139–1143. doi:10.1126/science.1116995

    Article  PubMed  CAS  Google Scholar 

  9. Martinac B (2004) Mechanosensitive ion channels: molecules of mechanotransduction. J Cell Sci 117(12):2449–2460. doi:10.1242/jcs.01232

    Article  PubMed  CAS  Google Scholar 

  10. Mammoto A, Mammoto T, Ingber DE (2008) Rho signaling and mechanical control of vascular development. Curr Opin Hematol 15(3):228–234. doi:10.1097/MOH.0b013e3282fa7445

    Article  PubMed  CAS  Google Scholar 

  11. Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, Kim SE, Schmidt M, Mathur J, Dubin AE, Montal M, Patapoutian A (2012) Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483(7388):176–181. doi:10.1038/nature10812

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Wehrle-Haller B (2007) Analysis of integrin dynamics by fluorescence recovery after photobleaching. Methods Mol Biol (Clifton, NJ) 370:173–202

    Article  CAS  Google Scholar 

  13. Hu K, Ji L, Applegate KT, Danuser G, Waterman-Storer CM (2007) Differential transmission of actin motion within focal adhesions. Science 315(5808):111–115. doi:10.1126/science.1135085

    Article  PubMed  CAS  Google Scholar 

  14. Brown CM, Hebert B, Kolin DL, Zareno J, Whitmore L, Horwitz AR, Wiseman PW (2006) Probing the integrin-actin linkage using high-resolution protein velocity mapping. J Cell Sci 119(24):5204–5214. doi:10.1242/jcs.03321

    Article  PubMed  CAS  Google Scholar 

  15. Hoffman BD, Grashoff C, Schwartz MA (2011) Dynamic molecular processes mediate cellular mechanotransduction. Nature 475(7356):316–323. doi:10.1038/nature10316

    Article  PubMed  CAS  Google Scholar 

  16. Jackson WF (2000) Ion channels and vascular tone. Hypertension 35(1):173–178

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Nilius B, Vriens J, Prenen J, Droogmans G, Voets T (2004) TRPV4 calcium entry channel: a paradigm for gating diversity. Am J Physiol Cell Physiol 286(2):C195–C205. doi:10.1152/ajpcell.00365.2003

    Article  PubMed  CAS  Google Scholar 

  18. Liedtke W, Kim C (2005) Functionality of the TRPV subfamily of TRP ion channels: add mechano-TRP and osmo-TRP to the lexicon! Cell Mol Life Sci 62(24):2985–3001. doi:10.1007/s00018-005-5181-5

    Article  PubMed  CAS  Google Scholar 

  19. Mendoza SA, Fang J, Gutterman DD, Wilcox DA, Bubolz AH, Li R, Suzuki M, Zhang DX (2010) TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress. Am J Physiol Heart Circ Physiol 298(2):H466–H476. doi:10.1152/ajpheart.00854.2009

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Hartmannsgruber V, Heyken WT, Kacik M, Kaistha A, Grgic I, Harteneck C, Liedtke W, Hoyer J, Kohler R (2007) Arterial response to shear stress critically depends on endothelial TRPV4 expression. PLoS One 2(9):e827. doi:10.1371/journal.pone.0000827

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Baratchi S, Tovar-Lopez FJ, Khoshmanesh K, Grace MS, Darby W, Almazi J, Mitchell A, McIntyre P (2014) Examination of the role of transient receptor potential vanilloid type 4 in endothelial responses to shear forces. Biomicrofluidics 8(4):044117. doi:10.1063/1.4893272

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Misonou H, Mohapatra DP, Park EW, Leung V, Zhen DK, Misonou K, Anderson AE, Trimmer JS (2004) Regulation of ion channel localization and phosphorylation by neuronal activity. Nat Neurosci 7(7):711–718. doi:10.1038/nn1260

    Article  PubMed  CAS  Google Scholar 

  23. Magoski NS, Kaczmarek LK (1998) Direct and indirect regulation of a single ion channel. J Physiol Lond 509(1):1. doi:10.1111/j.1469-7793.1998.001bo.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. 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(24):5659–5669. doi:10.1038/sj.emboj.7601429

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Xu H, Fu Y, Tian W, Cohen DM (2006) Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking. Am J Physiol Renal Physiol 290(5):F1103–F1109. doi:10.1152/ajprenal.00245.2005

    Article  PubMed  CAS  Google Scholar 

  26. Arniges M, Fernandez-Fernandez JM, Albrecht N, Schaefer 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. doi:10.1074/jbc.M511456200

    Article  PubMed  CAS  Google Scholar 

  27. Lei L, Cao X, Yang F, Shi DJ, Tang YQ, Zheng J, Wang K (2013) A TRPV4 channel C-terminal folding recognition domain critical for trafficking and function. J Biol Chem 288(15):10427–10439. doi:10.1074/jbc.M113.457291

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Cayouette S, Boulay G (2007) Intracellular trafficking of TRP channels. Cell Calcium 42(2):225–232. doi:10.1016/j.ceca.2007.01.014

    Article  PubMed  CAS  Google Scholar 

  29. Wegierski T, Lewandrowski U, Mueller B, Sickmann A, Walz G (2009) Tyrosine phosphorylation modulates the activity of TRPV4 in response to defined stimuli. J Biol Chem 284(5):2923–2933. doi:10.1074/jbc.M805357200

    Article  PubMed  CAS  Google Scholar 

  30. Poole DP, Amadesi S, Veldhuis NA, Abogadie FC, Lieu T, Darby W, Liedtke W, Lew MJ, McIntyre P, Bunnett NW (2013) Protease-activated receptor 2 (PAR(2)) Protein and transient receptor potential vanilloid 4 (TRPV4) protein coupling is required for sustained inflammatory signaling. J Biol Chem 288(8):5790–5802. doi:10.1074/jbc.M112.438184

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Lu X, Gibbs JS, Hickman HD, David A, Dolan BP, Jin Y, Kranz DM, Bennink JR, Yewdell JW, Varma R (2012) Endogenous viral antigen processing generates peptide-specific MHC class I cell-surface clusters. Proc Natl Acad Sci USA 109(38):15407–15412. doi:10.1073/pnas.1208696109

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hoger JH, Ilyin VI, Forsyth S, Hoger A (2002) Shear stress regulates the endothelial Kir2.1 ion channel. Proc Natl Acad Sci USA 99(11):7780–7785. doi:10.1073/pnas.102184999

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Barbier C, Boycott H, Eichel C, Louault F, Dilanian G, Coulombe A, Hatem S, Balse E (2014) Shear-stress triggered voltage-gated Kv1.5 channels exocytosis is altered in overloaded atria. Fundam Clin Pharmacol 28:79

    Google Scholar 

  34. Oancea E, Wolfe JT, Clapham DE (2006) Functional TRPM7 channels accumulate at the plasma membrane in response to fluid flow. Circ Res 98(2):245–253. doi:10.1161/01.RES.0000200179.29375.cc

    Article  PubMed  CAS  Google Scholar 

  35. Thorneloe KS, Cheung M, Bao W, Alsaid H, Lenhard S, Jian MY, Costell M, Maniscalco-Hauk K, Krawiec JA, Olzinski A, Gordon E, Lozinskaya I, Elefante L, Qin P, Matasic DS, James C, Tunstead J, Donovan B, Kallal L, Waszkiewicz A, Vaidya K, Davenport EA, Larkin J, Burgert M, Casillas LN, Marquis RW, Ye G, Eidam HS, Goodman KB, Toomey JR, Roethke TJ, Jucker BM, Schnackenberg CG, Townsley MI, Lepore JJ, Willette RN (2012) An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Trans Med 4(159):159ra148. doi:10.1126/scitranslmed.3004276

    Article  CAS  Google Scholar 

  36. Sciaky N, Presley J, Smith C, Zaal KJ, Cole N, Moreira JE, Terasaki M, Siggia E, Lippincott-Schwartz J (1997) Golgi tubule traffic and the effects of brefeldin A visualized in living cells. J Cell Biol 139(5):1137–1155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Deborde S, Perret E, Gravotta D, Deora A, Salvarezza S, Schreiner R, Rodriguez-Boulan E (2008) Clathrin is a key regulator of basolateral polarity. Nature 452(7188):719–723. doi:10.1038/nature06828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Sandvig K, van Deurs B (2002) Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett 529(1):49–53

    Article  PubMed  CAS  Google Scholar 

  39. De Matteis MA, Luini A (2008) Exiting the Golgi complex. Nat Rev Mol Cell Biol 9(4):273–284. doi:10.1038/nrm2378

    Article  PubMed  CAS  Google Scholar 

  40. Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T (2006) Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell 10(6):839–850. doi:10.1016/j.devcel.2006.04.002

    Article  PubMed  CAS  Google Scholar 

  41. Lazaro-Dieguez F, Colonna C, Cortegano M, Calvo M, Martinez SE, Egea G (2007) Variable actin dynamics requirement for the exit of different cargo from the trans-Golgi network. FEBS Lett 581(20):3875–3881. doi:10.1016/j.febslet.2007.07.015

    Article  PubMed  CAS  Google Scholar 

  42. Becker D, Bereiter-Hahn J, Jendrach M (2009) Functional interaction of the cation channel transient receptor potential vanilloid 4 (TRPV4) and actin in volume regulation. Eur J Cell Biol 88(3):141–152. doi:10.1016/j.ejcb.2008.10.002

    Article  PubMed  CAS  Google Scholar 

  43. Fan HC, Zhang X, McNaughton PA (2009) Activation of the TRPV4 ion channel is enhanced by phosphorylation. J Biol Chem 284(41):27884–27891. doi:10.1074/jbc.M109.028803

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. 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(28):20306–20314. doi:10.1074/jbc.M113.466797

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Lu HZ, Fedak PWM, Dai XJ, Du CQ, Zhou YQ, Henkelman M, Mongroo PS, Lau A, Yamabi H, Hinek A, Husain M, Hannigan G, Coles JG (2006) Integrin-linked kinase expression is elevated in human cardiac hypertrophy and induces hypertrophy in transgenic mice. Circulation 114(21):2271–2279. doi:10.1161/circulationaha.106.642330

    Article  PubMed  CAS  Google Scholar 

  46. Hannigan GE, LeungHagesteijn C, FitzGibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S (1996) Regulation of cell adhesion and anchorage-dependent growth by a new beta(1)-integrin-linked protein kinase. Nature 379(6560):91–96. doi:10.1038/379091a0

    Article  PubMed  CAS  Google Scholar 

  47. Lee SL, Hsu EC, Chou CC, Chuang HC, Bai LY, Kulp SK, Chen CS (2011) Identification and characterization of a novel integrin-linked kinase inhibitor. J Med Chem 54(18):6364–6374. doi:10.1021/jm2007744

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437(7057):426–431. doi:10.1038/nature03952

    Article  PubMed  CAS  Google Scholar 

  49. Tzima E, del Pozo MA, Shattil SJ, Chien S, Schwartz MA (2001) Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. EMBO J 20(17):4639–4647. doi:10.1093/emboj/20.17.4639

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Raftopoulou M, Hall A (2004) Cell migration: rho GTPases lead the way. Dev Biol 265(1):23–32. doi:10.1016/j.ydbio.2003.06.003

    Article  PubMed  CAS  Google Scholar 

  51. Baumer Y, Spindler V, Werthmann RC, Buenemann M, Waschke J (2009) Role of Rac 1 and cAMP in endothelial barrier stabilization and thrombin-induced barrier breakdown. J Cell Physiol 220(3):716–726. doi:10.1002/jcp.21819

    Article  PubMed  CAS  Google Scholar 

  52. Rebecca Soffe, Sara Baratchi, Shiyang Tang, Mahyar Nasabi, Peter McIntyre, Arnan Mitchell, Khashayar K (2015) Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis. Sci Rep. doi:10.1038/srep11973

    Google Scholar 

  53. Jaiswal JK, Rivera VM, Simon SM (2009) Exocytosis of post-Golgi vesicles is regulated by components of the endocytic machinery. Cell 137(7):1308–1319. doi:10.1016/j.cell.2009.04.064

    Article  PubMed  PubMed Central  Google Scholar 

  54. Tomes CN (2015) The proteins of exocytosis: lessons from the sperm model. Biochem J 465(3):359–370. doi:10.1042/bj20141169

    Article  PubMed  CAS  Google Scholar 

  55. Chen JL, Ahluwalia JP, Stamnes M (2002) Selective effects of calcium chelators on anterograde and retrograde protein transport in the cell. J Biol Chem 277(38):35682–35687. doi:10.1074/jbc.M204157200

    Article  PubMed  CAS  Google Scholar 

  56. Porat A, Elazar Z (2000) Regulation of intra-Golgi membrane transport by calcium. J Biol Chem 275(38):29233–29237. doi:10.1074/jbc.M005316200

    Article  PubMed  CAS  Google Scholar 

  57. Hutcheson IR, Griffith TM (1997) Central role of intracellular calcium stores in acute flow- and agonist-evoked endothelial nitric oxide release. Br J Pharmacol 122(1):117–125. doi:10.1038/sj.bjp.0701340

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Koo A, Nordsletten D, Umeton R, Yankama B, Ayyadurai S, Garcia-Cardena G, Dewey CF Jr (2013) In silico modeling of shear-stress-induced nitric oxide production in endothelial cells through systems biology. Biophys J 104(10):2295–2306. doi:10.1016/j.bpj.2013.03.052

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Jones SM, Howell KE, Henley JR, Cao H, McNiven MA (1998) Role of dynamin in the formation of transport vesicles from the trans-Golgi network. Science 279(5350):573–577. doi:10.1126/science.279.5350.573

    Article  PubMed  CAS  Google Scholar 

  60. Liu X, Bandyopadhyay BC, Nakamoto T, Singh B, Liedtke W, Melvin JE, Ambudkar I (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(22):15485–15495. doi:10.1074/jbc.M600549200

    Article  PubMed  CAS  Google Scholar 

  61. Becker D, Blase C, Bereiter-Hahn J, Jendrach M (2005) TRPV4 exhibits a functional role in cell-volume regulation. J Cell Sci 118(Pt 11):2435–2440. doi:10.1242/jcs.02372

    Article  PubMed  CAS  Google Scholar 

  62. Alenghat FJ, Nauli SM, Kolb R, Zhou J, Ingber DE (2004) Global cytoskeletal control of mechanotransduction in kidney epithelial cells. Exp Cell Res 301(1):23–30. doi:10.1016/j.yexcr.2004.08.003

    Article  PubMed  CAS  Google Scholar 

  63. 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. PLoS One 5(7):e11654. doi:10.1371/journal.pone.0011654

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Ridley AJ (2001) Rho proteins: linking signaling with membrane trafficking. Traffic (Copenhagen, Denmark) 2(5):303–310

    Article  CAS  Google Scholar 

  65. Symons M, Rusk N (2003) Control of vesicular trafficking by Rho GTPases. Curr Biol CB 13(10):R409–R418

    Article  PubMed  CAS  Google Scholar 

  66. Fiorio Pla A, Ong HL, Cheng KT, Brossa A, Bussolati B, Lockwich T, Paria B, Munaron L, Ambudkar IS (2012) TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling. Oncogene 31(2):200–212. doi:10.1038/onc.2011.231

    Article  PubMed  CAS  Google Scholar 

  67. Kawasaki J, Davis GE, Davis MJ (2004) Regulation of Ca2+-dependent K+ current by alphavbeta3 integrin engagement in vascular endothelium. J Biol Chem 279(13):12959–12966. doi:10.1074/jbc.M313791200

    Article  PubMed  CAS  Google Scholar 

  68. Chao JT, Gui P, Zamponi GW, Davis GE, Davis MJ (2011) Spatial association of the Cav1.2 calcium channel with alpha5beta1-integrin. Am J Physiol Cell Physiol 300(3):C477–C489. doi:10.1152/ajpcell.00171.2010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Carlson SS, Valdez G, Sanes JR (2010) Presynaptic calcium channels and alpha3-integrins are complexed with synaptic cleft laminins, cytoskeletal elements and active zone components. J Neurochem 115(3):654–666. doi:10.1111/j.1471-4159.2010.06965.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Thodeti CK, Matthews B, Ravi A, Mammoto A, Ghosh K, Bracha AL, Ingber DE (2009) TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ Res 104(9):1123–1130. doi:10.1161/circresaha.108.192930

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Ho B, Bendeck MP (2009) Integrin linked kinase (ILK) expression and function in vascular smooth muscle cells. Cell Adh Migr 3(2):174–176. doi:10.4161/cam.3.2.7374

    Article  PubMed  PubMed Central  Google Scholar 

  72. Dedhar S, Williams B, Hannigan G (1999) Integrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling. Trends Cell Biol 9(8):319–323

    Article  PubMed  CAS  Google Scholar 

  73. Tu YZ, Huang Y, Zhang YJ, Hua Y, Wu CY (2001) A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading. J Cell Biol 153(3):585–598. doi:10.1083/jcb.153.3.585

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Troussard AA, Mawji NM, Ong C, Mui A, St Arnaud R, Dedhar S (2003) Conditional knock-out of integrin-linked kinase demonstrates an essential role in protein kinase B/Akt activation. J Biol Chem 278(25):22374–22378. doi:10.1074/jbc.M303083200

    Article  PubMed  CAS  Google Scholar 

  75. Bellis A, Castaldo D, Trimarco V, Monti MG, Chivasso P, Sadoshima J, Trimarco B, Morisco C (2009) Cross-talk between PKA and Akt protects endothelial cells from apoptosis in the late ischemic preconditioning. Arterioscler Thromb Vasc Biol 29(8):1207–1212. doi:10.1161/atvbaha.109.184135

    Article  PubMed  CAS  Google Scholar 

  76. Hu Z, Xiong Y, Han X, Geng C, Jiang B, Huo Y, Luo J (2013) acute mechanical stretch promotes eNOS Activation in venous endothelial cells mainly via PKA and Akt pathways. PLoS One. doi:10.1371/journal.pone.0071359

    Google Scholar 

  77. Wu CY, Dedhar S (2001) Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol 155(4):505–510. doi:10.1083/jcb.200108077

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Wierzbicka-Patynowski I, Niewiarowski S, Marcinkiewicz C, Calvete JJ, Marcinkiewicz MM, McLane MA (1999) Structural requirements of echistatin for the recognition of alpha(v)beta(3) and alpha(5)beta(1) integrins. J Biol Chem 274(53):37809–37814

    Article  PubMed  CAS  Google Scholar 

  79. Nilius B, Voets T (2013) The puzzle of TRPV4 channelopathies. EMBO Rep 14(2):152–163. doi:10.1038/embor.2012.219

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. O’Conor CJ, Leddy HA, Benefield HC, Liedtke WB, Guilak F (2014) TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Natl Acad Sci USA 111(4):1316–1321. doi:10.1073/pnas.1319569111

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Pochynyuk O, Zaika O, O’Neil RG, Mamenko M (2013) Novel insights into TRPV4 function in the kidney. Pflugers Arch 465(2):177–186. doi:10.1007/s00424-012-1190-z

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Chen L, Kassmann M, Sendeski M, Tsvetkov D, Marko L, Michalick L, Riehle M, Liedtke WB, Kuebler WM, Harteneck C, Tepel M, Patzak A, Gollasch M (2015) Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature. Acta Physiol 213(2):481–491. doi:10.1111/apha.12355

    Article  CAS  Google Scholar 

  83. Sonkusare SK, Dalsgaard T, Bonev AD, Hill-Eubanks DC, Kotlikoff MI, Scott JD, Santana LF, Nelson MT (2014) AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension. Sci Signal 7(333):14. doi:10.1126/scisignal.2005052

    Article  CAS  Google Scholar 

  84. Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI, Heppner TJ, Hill-Eubanks DC, Nelson MT (2012) Elementary Ca2 + signals through endothelial TRPV4 channels regulate vascular function. Science 336(6081):597–601. doi:10.1126/science.1216283

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Suzanne Rogers and Professor Nigel Bunnett for the critical reading of the manuscript. This research was supported by project funding from the Australian National Health and Medical Research Council (project Grant 1046860 to PMc).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter McIntyre.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baratchi, S., Almazi, J.G., Darby, W. et al. Shear stress mediates exocytosis of functional TRPV4 channels in endothelial cells. Cell. Mol. Life Sci. 73, 649–666 (2016). https://doi.org/10.1007/s00018-015-2018-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-015-2018-8

Keywords

Navigation