TRPV4 Ion Channel: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Vicky Zhou and Version 1 by Trine L. Toft‐Bertelsen.

The transient receptor potential vanilloid 4 channel (TRPV4) belongs to the mammalian TRP superfamily of cation channels. TRPV4 is ubiquitously expressed, activated by a disparate array of stimuli, interacts with a multitude of proteins, and is modulated by a range of post-translational modifications, the majority of which we are only just beginning to understand. Not surprisingly, a great number of physiological roles have emerged for TRPV4, as have various disease states that are attributable to the absence, or abnormal functioning, of this ion channel. This review will highlight structural features of TRPV4, endogenous and exogenous activators of the channel, and discuss the reported roles of TRPV4 in health and disease.

  • TRP channels
  • transiten receptor potential vanillin 4
  • TRPV4
  • TRPV ion channel
Please wait, diff process is still running!

References

  1. Loukin, S.; Su, Z.; Zhou, ; Kung, C. Forward Genetic Analysis Reveals Multiple Gating Mechanisms of TRPV4. J. Biol. Chem. 2010, 285, 19884–19890, doi:10.1074/jbc.m110.113936.
  2. Voets, T.; Prenen, J.; Vriens, J.; Watanabe, H.; Janssens, A.; Wissenbach, U.; Bödding, M.; Droogmans, G.; Nilius, B. Molecular Determinants of Permeation through the Cation Channel TRPV4. Biol. Chem. 2002, 277, 33704–33710, doi:10.1074/jbc.m204828200.
  3. Watanabe, H.; Vriens, J.; Suh, S.H.; Benham, C.D.; Droogmans, G.; Nilius, B. Heat-evoked Activation of TRPV4 Channels in a HEK293 Cell Expression System and in Native Mouse Aorta Endothelial Cells. Biol. Chem. 2002, 277, 47044–47051, doi:10.1074/jbc.m208277200.
  4. Delany, N.S.; Hurle, M.; Facer, P.; Alnadaf, T.; Plumpton, C.; Kinghorn, I.; See, C.G.; Costigan, M.; Anand, P.; Woolf, C.J.; et al. Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Genom. 2001, 4, 165–174, doi:10.1152/physiolgenomics.2001.4.3.165.
  5. Kiselyov, K.; Soyombo, A.A.; Muallem, S. TRPpathies. Physiol. 2007, 578, 641–653, doi:10.1113/jphysiol.2006.119024.
  6. Nilius, B.; Voets, T. The puzzle of TRPV4 channelopathies. EMBO Rep. 2013, 14, 152–163.
  7. Zubcevic, L. Temperature-sensitive transient receptor potential vanilloid channels: Structural insights into ligand-dependent activation. J. Pharmacol.2020, doi:10.1111/bph.15310.
  8. Strotmann, R.; Harteneck, C.; Nunnenmacher, K.; Schultz, G.; Plant, T.D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Cell Biol. 2000, 2, 695–702, doi:10.1038/35036318.
  9. Liedtke, W.; Choe, Y.; Martí-Renom, M.A.; Bell, A.M.; Denis, C.S.; Šali, A.; Hudspeth, A.J.; Friedman, J.M.; Heller, S. Vanilloid Receptor–Related Osmotically Activated Channel (VR-OAC), a Candidate Vertebrate Osmoreceptor. Cell 2000, 103, 525–535, doi:10.1016/s0092-8674(00)00143-4.
  10. Rosenbaum, T.; Benítez-Angeles, M.; Sánchez-Hernández, R.; Morales-Lázaro, S.L.; Hiriart, M.; E Morales-Buenrostro, L.; Torres-Quiroz, F. TRPV4: A Physio and Pathophysiologically Significant Ion Channel. J. Mol. Sci. 2020, 21, 3837, doi:10.3390/ijms21113837.
  11. Eid, S.R. Therapeutic targeting of TRP channels—The TR(i)P to pain relief. Top. Med. Chem. 2011, 11, 2118–2130.
  12. Holzer, P. TRP channels in the digestive system. Curr. Pharm. Biotechnol. 2011, 12, 24–34.
  13. Earley, S.; Heppner, T.J.; Nelson, M.T.; Brayden, J.E. TRPV4 forms a novel Ca2+ signaling complex with ryanodine receptors and BKCa channels. Res. 2005, 97, 1270–1279.
  14. Liu, N.; Wu, J.; Chen, Y.; Zhao, J. Channels that Cooperate with TRPV4 in the Brain. Mol. Neurosci. 2020, 70, 1–9, doi:10.1007/s12031-020-01574-z.
  15. Monaghan, K.; Mcnaughten, J.; McGahon, M.K.; Kelly, C.; Kyle, D.; Yong, P.H.; McGeown, J.G.; Curtis, T. Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium. PLoS ONE 2015, 10, e0128359, doi:10.1371/journal.pone.0128359.
  16. Ryskamp, D.A.; Jo, A.O.; Frye, A.M.; Vazquez-Chona, F.; Macaulay, N.; Thoreson, W.B.; Križaj, D. Swelling and Eicosanoid Metabolites Differentially Gate TRPV4 Channels in Retinal Neurons and Glia. Neurosci. 2014, 34, 15689–15700, doi:10.1523/jneurosci.2540-14.2014.
  17. Guarino, B.D.; Paruchuri, S.; Thodeti, C.K. The role of TRPV4 channels in ocular function and pathologies. Eye Res. 2020, 201, 108257, doi:10.1016/j.exer.2020.108257.
  18. Jo, A.O.; Lakk, M.; Frye, A.M.; Phuong, T.T.T.; Redmon, S.N.; Roberts, R.; Berkowitz, B.A.; Yarishkin, O.; Križaj, D. Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels. Natl. Acad. Sci. USA 2016, 113, 3885–3890, doi:10.1073/pnas.1515895113.
  19. Lapajne, L.; Lakk, M.; Yarishkin, O.; Gubeljak, L.; Hawlina, M.; Križaj, D. Polymodal Sensory Transduction in Mouse Corneal Epithelial Cells. Ophthalmol. Vis. Sci. 2020, 61, 2, doi:10.1167/iovs.61.4.2.
  20. Gradilone, S.A.; Masyuk, A.I.; Splinter, P.L.; Banales, J.M.; Huang, B.Q.; Tietz, P.S.; Masyuk, T.V.; LaRusso, N.F. Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion. Natl. Acad. Sci. USA 2007, 104, 19138–19143, doi:10.1073/pnas.0705964104.
  21. Gevaert, T.; Vriens, J.; Segal, A.; Everaerts, W.; Roskams, T.; Talavera, K.; Owsianik, G.; Liedtke, W.; Daelemans, D.; Dewachter, I.; et al. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. Clin. Investig. 2007, 117, 3453–3462, doi:10.1172/jci31766.
  22. Birder, L.A.; Kullmann, F.A.; Lee, H.; Barrick, S.; De Groat, W.; Kanai, A.; Caterina, M. Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat. Pharmacol. Exp. Ther. 2007, 323, 227–235, doi:10.1124/jpet.107.125435.
  23. Kaßmann, M.; Harteneck, C.; Zhu, Z.; Nürnberg, B.; Tepel, M.; Gollasch, M. Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney. Acta Physiol. 2013, 207, 546–564, doi:10.1111/apha.12051.
  24. Liedtke, W.; Friedman, J.M. Abnormal osmotic regulation in trpv4−/− mice. Natl. Acad. Sci. USA 2003, 100, 13698–136703.
  25. Bellono, N.W.; Bayrer, J.R.; Leitch, D.B.; Castro, J.; Zhang, C.; O’Donnell, T.A.; Julius, D. Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways. Cell 2017, 170, 185–198.e16.
  26. Boesmans, W.; Owsianik, G.; Tack, J.; Voets, T.; Berghe, P.V. TRP channels in neurogastroenterology: Opportunities for therapeutic intervention. J. Pharmacol. 2010, 162, 18–37, doi:10.1111/j.1476-5381.2010.01009.x.
  27. Chung, M.-K.; Lee, H.; Caterina, M.J. Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes. Biol. Chem. 2003, 278, 32037–32046, doi:10.1074/jbc.m303251200.
  28. Kochukov, M.Y.; McNearney, T.A.; Fu, Y.; Westlund, K.N. Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes. J. Physiol. Physiol. 2006, 291, C424–C432, doi:10.1152/ajpcell.00553.2005.
  29. Kochukov, M.Y.; McNearney, T.A.; Yin, H.; Zhang, L.; Ma, F.; Ponomareva, L.; Abshire, S.; Westlund, K.N. Tumor Necrosis Factor-Alpha (TNF-α) Enhances Functional Thermal and Chemical Responses of TRP Cation Channels in Human Synoviocytes. Pain 2009, 5, 49, doi:10.1186/1744-8069-5-49.
  30. Itoh, Y.; Hatano, N.; Hayashi, H.; Onozaki, K.; Miyazawa, K.; Muraki, K. An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes. J. Physiol. Physiol. 2009, 297, C1082–C1090, doi:10.1152/ajpcell.00204.2009.
  31. Lorenzo, I.M.; Liedtke, W.; Sanderson, M.J.; Valverde, M.A. TRPV4 channel participates in receptor-operated calcium entry and ciliary beat frequency regulation in mouse airway epithelial cells. Natl. Acad. Sci. USA 2008, 105, 12611–12616, doi:10.1073/pnas.0803970105.
  32. Pan, Z.; Yang, H.; Mergler, S.; Liu, H.; Tachado, S.D.; Zhang, F.; Kao, W.W.Y.; Koziel, H.; Pleyer, U.; Reinach, P. Dependence of regulatory volume decrease on transient receptor potential vanilloid 4 (TRPV4) expression in human corneal epithelial cells. Cell Calcium 2008, 44, 374–385, doi:10.1016/j.ceca.2008.01.008.
  33. Tian, W.; Salanova, M.; Xu, H.; Lindsley, J.N.; Oyama, T.T.; Anderson, S.; Bachmann, S.; Cohen, D.M. Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments. J. Physiol. Physiol. 2004, 287, F17–F24, doi:10.1152/ajprenal.00397.2003.
  34. Watanabe, H.; Davis, J.B.; Smart, D.; Jerman, J.C.; Smith, G.D.; Hayes, P.; Vriens, J.; Cairns, W.; Wissenbach, U.; Prenen, J.; et al. Activation of TRPV4 Channels (hVRL-2/mTRP12) by Phorbol Derivatives. Biol. Chem. 2002, 277, 13569–13577, doi:10.1074/jbc.m200062200.
  35. Vriens, J.; Watanabe, H.; Janssens, A.; Droogmans, G.; Voets, T.; Nilius, B. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Natl. Acad. Sci. USA 2004, 101, 396–401, doi:10.1073/pnas.0303329101.
  36. Filosa, J.A.; Yao, X.; Rath, G. TRPV4 and the Regulation of Vascular Tone. Cardiovasc. Pharmacol. 2013, 61, 113–119, doi:10.1097/fjc.0b013e318279ba42.
  37. Marrelli, S.P.; O’Neil, R.G.; Brown, R.C.; Bryan, R.M. PLA2 and TRPV4 channels regulate endothelial calcium in cerebral arteries. J. Physiol. Circ. Physiol. 2007, 292, H1390–H1397, doi:10.1152/ajpheart.01006.2006.
  38. Earley, S.; Pauyo, T.; Drapp, R.; Tavares, M.J.; Liedtke, W.; Brayden, J.E. TRPV4-dependent dilation of peripheral resistance arteries influences arterial pressure. J. Physiol. Circ. Physiol. 2009, 297, H1096–H1102, doi:10.1152/ajpheart.00241.2009.
  39. Alvarez, D.F.; King, J.A.; Weber, D.; Addison, E.; Liedtke, W.; Townsley, M.I. Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: A novel mechanism of acute lung injury. Res. 2006, 99, 988–995.
  40. Campbell, W.B.; Fleming, I. Epoxyeicosatrienoic acids and endothelium-dependent responses. Pflügers Arch. Eur. J. Physiol. 2010, 459, 881–895, doi:10.1007/s00424-010-0804-6.
  41. Martin, E.; Dahan, D.; Cardouat, G.; Gillibert-Duplantier, J.; Marthan, R.; Savineau, J.-P.; Ducret, T. Involvement of TRPV1 and TRPV4 channels in migration of rat pulmonary arterial smooth muscle cells. Pflügers Arch. 2012, 464, 261–272, doi:10.1007/s00424-012-1136-5.
  42. Yang, X.-R.; Lin, A.H.Y.; Hughes, J.M.; Flavahan, N.A.; Cao, Y.-N.; Liedtke, W.; Sham, J.S.K. Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension. J. Physiol. Cell. Mol. Physiol. 2012, 302, L555–L568, doi:10.1152/ajplung.00005.2011.
  43. Gao, F.; Wang, D.H. Hypotension induced by activation of the transient receptor potential vanilloid 4 channels: Role of Ca2+-activated K+ channels and sensory nerves. Hypertens. 2010, 28, 102–110, doi:10.1097/hjh.0b013e328332b865.
  44. Arniges, M.; Fernandez-Fernandez, J.M.; Albrecht, N.; Schaefer, M.; Valverde, M.A. Human TRPV4 channel splice variants revealed a key role of ankyrin domains in multimerization and trafficking. J. Chem. 2006, 281, 1580–1586.
  45. Shigematsu, H.; Sokabe, T.; Danev, R.; Tominaga, M.; Nagayama, K. A 3.5-nm Structure of Rat TRPV4 Cation Channel Revealed by Zernike Phase-contrast Cryoelectron Microscopy. Biol. Chem. 2010, 285, 11210–11218, doi:10.1074/jbc.m109.090712.
  46. Inada, H.; Procko, E.; Sotomayor, M.; Gaudet, R. Structural and Biochemical Consequences of Disease-Causing Mutations in the Ankyrin Repeat Domain of the Human TRPV4 Channel. Biochemistry 2012, 51, 6195–6206, doi:10.1021/bi300279b.
  47. Phelps, C.B.; Huang, R.J.; Lishko, P.V.; Wang, R.R.; Gaudet, R. Structural Analyses of the Ankyrin Repeat Domain of TRPV6 and Related TRPV Ion Channels. Biochemistry 2008, 47, 2476–2484, doi:10.1021/bi702109w.
  48. Everaerts, W.; Nilius, B.; Owsianik, G. The vanilloid transient receptor potential channel TRPV4: From structure to disease. Biophys. Mol. Biol. 2010, 103, 2–17, doi:10.1016/j.pbiomolbio.2009.10.002.
  49. Ma, X.; Cheng, K.-T.; Wong, C.-O.; O’Neil, R.G.; Birnbaumer, L.; Ambudkar, I.S.; Yao, X. Heteromeric TRPV4-C1 channels contribute to store-operated Ca2+ entry in vascular endothelial cells. Cell Calcium 2011, 50, 502–509, doi:10.1016/j.ceca.2011.08.006.
  50. Stewart, A.P.; Smith, G.D.; Sandford, R.N.; Edwardson, J.M. Atomic Force Microscopy Reveals the Alternating Subunit Arrangement of the TRPP2-TRPV4 Heterotetramer. J. 2010, 99, 790–797, doi:10.1016/j.bpj.2010.05.012.
  51. Du, J.; Ma, X.; Shen, B.; Huang, Y.; Birnbaumer, L.; Yao, X. TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel. FASEB J.2014, 28, 4677–4685, doi:10.1096/fj.14-251652.
  52. Watanabe, H.; Vriens, J.; Janssens, A.; Wondergem, R.; Droogmans, G.; Nilius, B. Modulation of TRPV4 gating by intra- and extracellular Ca2+. Cell Calcium 2003, 33, 489–495, doi:10.1016/s0143-4160(03)00064-2.
  53. Phuong, T.T.T.; Redmon, S.N.; Yarishkin, O.; Winter, J.M.; Li, D.Y.; Križaj, D. Calcium influx through TRPV4 channels modulates the adherens contacts between retinal microvascular endothelial cells. Physiol. 2017, 595, 6869–6885, doi:10.1113/jp275052.
  54. Toft-Bertelsen, T.L.; Križaj, D.; Macaulay, N. When size matters: Transient receptor potential vanilloid 4 channel as a volume-sensor rather than an osmo-sensor. Physiol. 2017, 595, 3287–3302, doi:10.1113/jp274135.
  55. Jo, A.O.; Ryskamp, D.A.; Phuong, T.T.T.; Verkman, A.S.; Yarishkin, O.; Macaulay, N.; Križaj, D. TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium Homeostasis in Retinal Muller Glia. Neurosci. 2015, 35, 13525–13537, doi:10.1523/jneurosci.1987-15.2015.
  56. Teng, J.; Loukin, S.H.; Anishkin, A.; Kung, C. L596–W733 bond between the start of the S4–S5 linker and the TRP box stabilizes the closed state of TRPV4 channel. Natl. Acad. Sci. USA 2015, 112, 3386–3391, doi:10.1073/pnas.1502366112.
  57. Güler, A.D.; Lee, H.; Iida, T.; Shimizu, I.; Tominaga, M.; Caterina, M. Heat-Evoked Activation of the Ion Channel, TRPV4. Neurosci. 2002, 22, 6408–6414, doi:10.1523/jneurosci.22-15-06408.2002.
  58. Berna-Erro, A.; Izquierdo-Serra, M.; Sepúlveda, R.V.; Rubio-Moscardo, F.; Doñate-Macián, P.; Serra, S.A.; Carrillo-Garcia, J.; Perálvarez-Marín, A.; González-Nilo, F.; Fernández-Fernández, J.M.; et al. Structural determinants of 5′,6′-epoxyeicosatrienoic acid binding to and activation of TRPV4 channel. Rep. 2017, 7, 10522, doi:10.1038/s41598-017-11274-1.
  59. Watanabe, H.; Vriens, J.; Prenen, J.; Droogmans, G.; Voets, T.; Nilius, B. Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Cell Biol. 2003, 424, 434–438, doi:10.1038/nature01807.
  60. Caires, R.; Sierra-Valdez, F.J.; Millet, J.R.; Herwig, J.D.; Roan, E.; Vásquez, V.; Cordero-Morales, J.F. Omega-3 Fatty Acids Modulate TRPV4 Function through Plasma Membrane Remodeling. Cell Rep. 2017, 21, 246–258, doi:10.1016/j.celrep.2017.09.029.
  61. Simpson, S.; Preston, D.; Schwerk, C.; Schroten, H.; Blazer-Yost, B. Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells. J. Physiol. Physiol. 2019, 317, C881–C893, doi:10.1152/ajpcell.00205.2019.
  62. Loukin, S.H.; Su, Z.; Kung, C. Hypotonic shocks activate rat TRPV4 in yeast in the absence of polyunsaturated fatty acids. FEBS Lett. 2009, 583, 754–758, doi:10.1016/j.febslet.2009.01.027.
  63. Toft-Bertelsen, T.L.; Yarishkin, O.; Redmon, S.; Phuong, T.T.T.; Križaj, D.; Macaulay, N. Volume sensing in the transient receptor potential vanilloid 4 ion channel is cell type–specific and mediated by an N-terminal volume-sensing domain. Biol. Chem. 2019, 294, 18421–18434, doi:10.1074/jbc.ra119.011187.
  64. Bang, S.; Yoo, S.; Yang, T.-J.; Cho, H.; Hwang, S.W. Farnesyl Pyrophosphate Is a Novel Pain-producing Molecule via Specific Activation of TRPV3. Biol. Chem. 2010, 285, 19362–19371, doi:10.1074/jbc.m109.087742.
  65. Bang, S.; Yoo, S.; Yang, T.-J.; Cho, H.; Hwang, S.W. Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels. Pain 2011, 152, 1156–1164, doi:10.1016/j.pain.2011.01.044.
  66. Okada, Y.; Maeno, E. Apoptosis, cell volume regulation and volume-regulatory chloride channels. Biochem. Physiol. Part A Mol. Integr. Physiol.2001, 130, 377–383, doi:10.1016/s1095-6433(01)00424-x.
  67. Nilius, B.; Prenen, J.; Wissenbach, U.; Bödding, M.; Droogmans, G. Differential activation of the volume-sensitive cation channel TRP12 (OTRPC4) and volume-regulated anion currents in HEK-293 cells. Pflügers Arch. 2001, 443, 227–233, doi:10.1007/s004240100676.
  68. Benfenati, V.; Caprini, M.; Dovizio, M.; Mylonakou, M.N.; Ferroni, S.; Ottersen, O.P.; Amiry-Moghaddam, M. An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proc. Natl. Acad. Sci. USA 2011, 108, 2563–2568.
  69. Galizia, L.; Pizzoni, A.; Fernandez, J.; Rivarola, V.; Capurro, C.; Ford, P. Functional interaction between AQP2 and TRPV4 in renal cells. Cell. Biochem.2012, 113, 580–589, doi:10.1002/jcb.23382.
  70. Iuso, A.; Križaj, D. TRPV4-AQP4 interactions ‘turbocharge’ astroglial sensitivity to small osmotic gradients. Channels 2016, 10, 172–174, doi:10.1080/19336950.2016.1140956.
  71. Liu, X.; Bandyopadhyay, B.C.; Nakamoto, T.; Singh, B.B.; Liedtke, W.; Melvin, J.E.; Ambudkar, I.S. A role for AQP5 in activation of TRPV4 by hypotonicity: Concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery. Biol. Chem. 2008, 283, 3688, doi:10.1016/s0021-9258(20)69833-7.
  72. Mola, M.G.; Sparaneo, A.; Gargano, C.D.; Spray, D.C.; Svelto, M.; Frigeri, A.; Scemes, E.; Nicchia, G.P. The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: A different point of view on the role of aquaporins. Glia 2016, 64, 139–154, doi:10.1002/glia.22921.
  73. Teng, J.; Loukin, S.; Zhou, X.; Kung, C. Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4. Vis. Exp. 2013, 2013, 82, doi:10.3791/50816.
  74. Schumacher, M.A.; Eilers, H. TRPV1 splice variants: Structure and function. Biosci. 2010, 15, 872–882.
  75. Sharif Naeini, R.; Witty, M.F.; Seguela, P.; Bourque, C.W. An N-terminal variant of Trpv1 channel is required for osmosensory transduction. Neurosci. 2006, 9, 93–98.
  76. Sudbury, J.R.; Ciura, S.; Sharif-Naeini, R.; Bourque, C.W. Osmotic and thermal control of magnocellular neurosecretory neurons--role of an N-terminal variant of trpv1. J. Neurosci. 2010, 32, 2022–2030.
  77. D’Hoedt, D.; Owsianik, G.; Prenen, J.; Cuajungco, M.P.; Grimm, C.; Heller, S.; Voets, T.; Nilius, B. Stimulus-specific Modulation of the Cation Channel TRPV4 by PACSIN 3. Biol. Chem. 2008, 283, 6272–6280, doi:10.1074/jbc.m706386200.
  78. Goswami, C.; Kuhn, J.; Heppenstall, P.A.; Hucho, T. Importance of Non-Selective Cation Channel TRPV4 Interaction with Cytoskeleton and Their Reciprocal Regulations in Cultured Cells. PLoS ONE 2010, 5, e11654, doi:10.1371/journal.pone.0011654.
  79. Becker, D.; Bereiter-Hahn, J.; Jendrach, M. Functional interaction of the cation channel transient receptor potential vanilloid 4 (TRPV4) and actin in volume regulation. J. Cell Biol. 2009, 88, 141–152, doi:10.1016/j.ejcb.2008.10.002.
  80. Ramadass, R.; Becker, D.; Jendrach, M.; Bereiter-Hahn, J. Spectrally and spatially resolved fluorescence lifetime imaging in living cells: TRPV4–microfilament interactions. Biochem. Biophys. 2007, 463, 27–36, doi:10.1016/j.abb.2007.01.036.
  81. Ji, C.; McCulloch, C.A. TRPV4 integrates matrix mechanosensing with Ca2+ signaling to regulate extracellular matrix remodeling. FEBS J. 2020, doi:10.1111/febs.15665.
  82. Garcia-Elias, A.; Mrkonjić, S.; Pardo-Pastor, C.; Inada, H.; Hellmich, U.A.; Rubio-Moscardó, F.; Plata, C.; Gaudet, R.; Vicente, R.; Valverde, M.A. Phosphatidylinositol-4,5-biphosphate-dependent rearrangement of TRPV4 cytosolic tails enables channel activation by physiological stimuli. Natl. Acad. Sci. USA 2013, 110, 9553–9558, doi:10.1073/pnas.1220231110.
  83. Alessandri-Haber, N.; Yeh, J.J.; Boyd, A.E.; Parada, C.A.; Chen, X.; Reichling, D.B.; Levine, J.D. Hypotonicity Induces TRPV4-Mediated Nociception in Rat. Neuron 2003, 39, 497–511, doi:10.1016/s0896-6273(03)00462-8.
  84. Boudaka, A.; Al-Yazeedi, M.; Al-Lawati, I. Role of Transient Receptor Potential Vanilloid 4 Channel in Skin Physiology and Pathology. Sultan Qaboos Univ. Med. J. 2020, 20, 138–146, doi:10.18295/squmj.2020.20.02.003.
  85. Choi, J.E.; Di Nardo, A. Skin neurogenic inflammation. Immunopathol. 2018, 40, 249–259, doi:10.1007/s00281-018-0675-z.
  86. Shibasaki, K.; Suzuki, M.; Mizuno, A.; Tominaga, M. Effects of Body Temperature on Neural Activity in the Hippocampus: Regulation of Resting Membrane Potentials by Transient Receptor Potential Vanilloid 4. Neurosci. 2007, 27, 1566–1575, doi:10.1523/jneurosci.4284-06.2007.
  87. Matsumoto, H.; Sugio, S.; Seghers, F.; Križaj, D.; Akiyama, H.; Ishizaki, Y.; Gailly, P.; Shibasaki, K. Retinal Detachment-Induced Müller Glial Cell Swelling Activates TRPV4 Ion Channels and Triggers Photoreceptor Death at Body Temperature. Neurosci. 2018, 38, 8745–8758, doi:10.1523/jneurosci.0897-18.2018.
  88. Caterina, M.J.; Rosen, T.A.; Tominaga, M.; Brake, A.J.; Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat. Cell Biol.1999, 398, 436–441, doi:10.1038/18906.
  89. Lakk, M.; Yarishkin, O.; Baumann, J.M.; Iuso, A.; Križaj, D. Cholesterol regulates polymodal sensory transduction in Müller glia. Glia 2017, 65, 2038–2050, doi:10.1002/glia.23213.
  90. Lawhorn, B.G.; Brnardic, E.J.; Behm, D.J. Recent advances in TRPV4 agonists and antagonists. Med. Chem. Lett. 2020, 30, 127022, doi:10.1016/j.bmcl.2020.127022.
  91. Vriens, J.; Owsianik, G.; Janssens, A.; Voets, T.; Nilius, B. Determinants of 4α-Phorbol Sensitivity in Transmembrane Domains 3 and 4 of the Cation Channel TRPV4. Biol. Chem. 2007, 282, 12796–12803, doi:10.1074/jbc.m610485200.
  92. Vincent, F.; Acevedo, A.; Nguyen, M.T.; Dourado, M.; DeFalco, J.; Gustafson, A.; Spiro, P.; Emerling, D.E.; Kelly, M.G.; Duncton, M.A.J. Identification and characterization of novel TRPV4 modulators. Biophys. Res. Commun. 2009, 389, 490–494, doi:10.1016/j.bbrc.2009.09.007.
  93. Klausen, T.K.; Pagani, A.; Minassi, A.; Ech-Chahad, A.; Prenen, J.; Owsianik, G.; Hoffmann, E.K.; Pedersen, S.F.; Appendino, G.; Nilius, B. Modulation of the Transient Receptor Potential Vanilloid Channel TRPV4 by 4α-Phorbol Esters: A Structure−Activity Study. Med. Chem. 2009, 52, 2933–2939, doi:10.1021/jm9001007.
  94. Klausen, T.K.; Janssens, A.; Prenen, J.; Owsianik, G.; Hoffmann, E.K.; Pedersen, S.F.; Nilius, B. Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity: Implications for the role of the pore region in regulating TRPV4 activity. Cell Calcium 2014, 55, 38–47, doi:10.1016/j.ceca.2013.11.001.
  95. Alexander, R.; Kerby, A.; Aubdool, A.A.; Power, A.R.; Grover, S.; Gentry, C.; Grant, A.D. 4α-phorbol 12,13-didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4. J. Pharmacol. 2013, 168, 761–772, doi:10.1111/j.1476-5381.2012.02186.x.
  96. Thorneloe, K.S.; Sulpizio, A.C.; Lin, Z.; Figueroa, D.J.; Clouse, A.K.; McCafferty, G.P.; Chendrimada, T.P.; Lashinger, E.S.; Gordon, E.; Evans, L.; et al. N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: Part I. Pharmacol. Exp. Ther. 2008, 326, 432–442.
  97. Jin, M.; Wu, Z.; Chen, L.; Jaimes, J.; Collins, D.; Walters, E.T.; O’Neil, R.G. Determinants of TRPV4 Activity following Selective Activation by Small Molecule Agonist GSK1016790A. PLoS ONE 2011, 6, e16713, doi:10.1371/journal.pone.0016713.
  98. Berrier, C.; Coulombe, A.; Szabo, I.; Zoratti, M.; Ghazi, A. Gadolinium ion inhibits loss of metabolites induced by osmotic shock and large stretch-activated channels in bacteria. JBIC J. Biol. Inorg. Chem. 1992, 206, 559–565, doi:10.1111/j.1432-1033.1992.tb16960.x.
  99. Vincent, F.; Duncton, M.A. TRPV4 agonists and antagonists. Top. Med. Chem. 2011, 11, 2216–2226.
  100. Kittaka, H.; Yamanoi, Y.; Tominaga, M. Transient receptor potential vanilloid 4 (TRPV4) channel as a target of crotamiton and its bimodal effects. Pflügers Arch. 2017, 469, 1313–1323, doi:10.1007/s00424-017-1998-7.
  101. Everaerts, W.; Zhen, X.; Ghosh, D.; Vriens, J.; Gevaert, T.; Gilbert, J.P.; Hayward, N.J.; McNamara, C.R.; Xue, F.; Moran, M.M.; et al. Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Natl. Acad. Sci. USA 2010, 107, 19084–19089, doi:10.1073/pnas.1005333107.
  102. Wang, Y.; Fu, X.; Gaiser, S.; Köttgen, M.; Kramer-Zucker, A.; Walz, G.; Wegierski, T. OS-9 Regulates the Transit and Polyubiquitination of TRPV4 in the Endoplasmic Reticulum. Biol. Chem. 2007, 282, 36561–36570, doi:10.1074/jbc.m703903200.
  103. Shin, S.H.; Lee, E.J.; Chun, J.; Hyun, S.; Kang, S.S. Phosphorylation on TRPV4 Serine 824 Regulates Interaction with STIM1. Open Biochem. J. 2015, 9, 24–33, doi:10.2174/1874091x01509010024.
  104. Doñate-Macián, P.; Enrich-Bengoa, J.; Degano, I.R.; Quintana, D.G.; Perálvarez-Marín, A. Trafficking of Stretch-Regulated TRPV2 and TRPV4 Channels Inferred Through Interactomics. Biomolecules 2019, 9, 791, doi:10.3390/biom9120791.
  105. Wegierski, T.; Hill, K.; Schaefer, M.; Walz, G. The HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels. EMBO J. 2006, 25, 5659–5669, doi:10.1038/sj.emboj.7601429.
  106. Shukla, A.K.; Kim, J.; Ahn, S.; Xiao, K.; Shenoy, S.K.; Liedtke, W.; Lefkowitz, R.J. Arresting a transient receptor potential (TRP) channel: Beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4. Biol. Chem. 2010, 285, 30115–30125.
  107. Cao, S.; Anishkin, A.; Zinkevich, N.S.; Nishijima, Y.; Korishettar, A.; Wang, Z.; Fang, J.; Wilcox, D.A.; Zhang, D.X. Transient receptor potential vanilloid 4 (TRPV4) activation by arachidonic acid requires protein kinase A–mediated phosphorylation. Biol. Chem. 2018, 293, 5307–5322, doi:10.1074/jbc.m117.811075.
  108. Fan, H.-C.; Zhang, X.; McNaughton, P.A. Activation of the TRPV4 Ion Channel Is Enhanced by Phosphorylation. Biol. Chem. 2009, 284, 27884–27891, doi:10.1074/jbc.m109.028803.
  109. Peng, H.; Lewandrowski, U.; Müller, B.; Sickmann, A.; Walz, G.; Wegierski, T. Identification of a Protein Kinase C-dependent phosphorylation site involved in sensitization of TRPV4 channel. Biophys. Res. Commun. 2010, 391, 1721–1725, doi:10.1016/j.bbrc.2009.12.140.
  110. Strotmann, R.; Semtner, M.; Kepura, F.; Plant, T.D.; Schoneberg, T. Interdomain Interactions Control Ca2+-Dependent Potentiation in the Cation Channel TRPV4. PLoS ONE 2010, 5, e10580, doi:10.1371/journal.pone.0010580.
  111. Shibasaki, K. TRPV4 activation by thermal and mechanical stimuli in disease progression. Investig. 2020, 100, 218–223, doi:10.1038/s41374-019-0362-2.
  112. Suzuki, M.; Mizuno, A.; Kodaira, K.; Imai, M. Impaired Pressure Sensation in Mice Lacking TRPV4. Biol. Chem. 2003, 278, 22664–22668, doi:10.1074/jbc.m302561200.
  113. Vriens, J.; Owsianik, G.; Fisslthaler, B.; Suzuki, M.; Janssens, A.; Voets, T.; Morisseau, C.; Hammock, B.D.; Fleming, I.; Busse, R.; et al. Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium. Circ Res. 2005, 97, 908–915.
  114. Sonkusare, S.K.; Bonev, A.D.; LeDoux, J.; Liedtke, W.; Kotlikoff, M.I.; Heppner, T.J.; Hill-Eubanks, D.C.; Nelson, M.T. Elementary Ca2+ Signals Through Endothelial TRPV4 Channels Regulate Vascular Function. Science 2012, 336, 597–601, doi:10.1126/science.1216283.
  115. Liedtke, W.B. Molecular Mechanisms of TRPV4-Mediated Neural Signaling. N. Y. Acad. Sci. 2008, 1144, 42–52, doi:10.1196/annals.1418.012.
  116. Cortright, D.N.; Szallasi, A. TRP Channels and Pain. Pharm. Des. 2009, 15, 1736–1749, doi:10.2174/138161209788186308.
  117. Tabuchi, K.; Suzuki, M.; Mizuno, A.; Hara, A. Hearing impairment in TRPV4 knockout mice. Lett. 2005, 382, 304–308, doi:10.1016/j.neulet.2005.03.035.
  118. Masuyama, R.; Vriens, J.; Voets, T.; Karashima, Y.; Owsianik, G.; Vennekens, R.; Lieben, L.; Torrekens, S.; Moermans, K.; Bosch, A.V.; et al. TRPV4-Mediated Calcium Influx Regulates Terminal Differentiation of Osteoclasts. Cell Metab. 2008, 8, 257–265, doi:10.1016/j.cmet.2008.08.002.
  119. Masuyama, R.; Mizuno, A.; Komori, H.; Kajiya, H.; Uekawa, A.; Kitaura, H.; Okabe, K.; Ohyama, K.; Komori, T. Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass. Bone Miner. Res. 2012, 27, 1708–1721, doi:10.1002/jbmr.1629.
  120. Atobe, M. Activation of Transient Receptor Potential Vanilloid (TRPV) 4 as a Therapeutic Strategy in Osteoarthritis. Top. Med. Chem. 2019, 19, 2254–2267, doi:10.2174/1568026619666191010162850.
  121. Okuhara, D.Y.; Hsia, A.Y.; Xie, M. Transient receptor potential channels as drug targets. Expert Opin. Ther. Targets 2007, 11, 391–401, doi:10.1517/14728222.11.3.391.
  122. Sałat, K.; Moniczewski, A.; Librowski, T. Transient receptor potential channels—Emerging novel drug targets for the treatment of pain. Med. Chem.2013, 20, 1409–1436, doi:10.2174/09298673113209990107.
  123. Nishimura, G.; Lausch, E.; Savarirayan, R.; Shiba, M.; Spranger, J.; Zabel, B.; Ikegawa, S.; Superti-Furga, A.; Unger, S. TRPV4-associated skeletal dysplasias. J. Med. Genet. Part. C Semin. Med. Genet. 2012, 160, 190–204, doi:10.1002/ajmg.c.31335.
  124. Lamandé, S.R.; Yuan, Y.; Gresshoff, I.L.; Rowley, L.; Belluoccio, D.; Kaluarachchi, K.; Little, C.B.; Botzenhart, E.; Zerres, K.; Amor, D.J.; et al. Mutations in TRPV4 cause an inherited arthropathy of hands and feet. Genet. 2011, 43, 1142–1146.
  125. Nilius, B.; Owsianik, G. Channelopathies converge on TRPV4. Genet. 2010, 42, 98–100, doi:10.1038/ng0210-98.
  126. Velilla, J.; Marchetti, M.M.; Toth-Petroczy, A.; Grosgogeat, C.; Bennett, A.H.; Carmichael, N.; Estrella, E.; Darras, B.T.; Frank, N.Y.; Krier, J.; et al. Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis. Genet. 2019, 5, e312, doi:10.1212/nxg.0000000000000312.
  127. Loukin, S.; Zhou, X.; Su, Z.; Saimi, Y.; Kung, C. Wild-type and Brachyolmia-causing Mutant TRPV4 Channels Respond Directly to Stretch Force. Biol. Chem. 2010, 285, 27176–27181, doi:10.1074/jbc.m110.143370.
  128. McNulty, A.L.; Leddy, H.A.; Liedtke, W.B.; Guilak, F. TRPV4 as a therapeutic target for joint diseases. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2014, 388, 437–450, doi:10.1007/s00210-014-1078-x.
  129. Nemec, S.F.; Cohn, D.H.; Krakow, D.; Funari, V.A.; Rimoin, D.L.; Lachman, R.S. The importance of conventional radiography in the mutational analysis of skeletal dysplasias (the TRPV4 mutational family). Radiol. 2011, 42, 15–23, doi:10.1007/s00247-011-2229-6.
  130. Loukin, S.; Su, Z.; Kung, C. Increased Basal Activity Is a Key Determinant in the Severity of Human Skeletal Dysplasia Caused by TRPV4 Mutations. PLoS ONE 2011, 6, e19533, doi:10.1371/journal.pone.0019533.
  131. Cho, T.-J.; Matsumoto, K.; Fano, V.; Dai, J.; Kim, O.-H.; Chae, J.H.; Yoo, W.J.; Tanaka, Y.; Matsui, Y.; Takigami, I.; et al. TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: A report of three patients. J. Med. Genet. Part. A 2012, 158, 795–802, doi:10.1002/ajmg.a.35268.
  132. Dai, J.; Cho, T.-J.; Unger, S.; Lausch, E.; Nishimura, G.; Kim, O.-H.; Superti-Furga, A.; Ikegawa, S. TRPV4-pathy, a novel channelopathy affecting diverse systems. Hum. Genet. 2010, 55, 400–402, doi:10.1038/jhg.2010.37.
  133. Camacho, N.; Krakow, D.; Johnykutty, S.; Katzman, P.J.; Pepkowitz, S.; Vriens, J.; Nilius, B.; Boyce, B.F.; Cohn, D.H. DominantTRPV4mutations in nonlethal and lethal metatropic dysplasia. J. Med. Genet. Part. A 2010, 152, 1169–1177, doi:10.1002/ajmg.a.33392.
  134. Krakow, D.; Vriens, J.; Camacho, N.; Luong, P.; Deixler, H.; Funari, T.L.; Bacino, C.A.; Irons, M.B.; Holm, I.A.; Sadler, L.; et al. Mutations in the Gene Encoding the Calcium-Permeable Ion Channel TRPV4 Produce Spondylometaphyseal Dysplasia, Kozlowski Type and Metatropic Dysplasia. J. Hum. Genet. 2009, 84, 307–315, doi:10.1016/j.ajhg.2009.01.021.
  135. Kang, S.S.; Shin, S.H.; Auh, C.-K.; Chun, J. Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation. Mol. Med. 2012, 44, 707–722, doi:10.3858/emm.2012.44.12.080.
  136. Fawcett, K.A.; Murphy, S.M.; Polke, J.M.; Wray, S.; Burchell, V.S.; Manji, H.; Quinlivan, R.M.; Zdebik, A.A.; Reilly, M.M.; Houlden, H. Comprehensive analysis of theTRPV4gene in a large series of inherited neuropathies and controls. Neurol. Neurosurg. Psychiatry 2012, 83, 1204–1209, doi:10.1136/jnnp-2012-303055.
  137. Nishimura, G.; Dai, J.; Lausch, E.; Unger, S.; Mégarbané, A.; Kitoh, H.; Kim, O.H.; Cho, T.-J.; Bedeschi, F.; Benedicenti, F.; et al. Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. J. Med. Genet. Part. A2010, 152, 1443–1449, doi:10.1002/ajmg.a.33414.
  138. Unger, S.; Lausch, E.; Stanzial, F.; Gillessen-Kaesbach, G.; Stefanova, I.; Di Stefano, C.M.; Bertini, E.; Dionisi-Vici, C.; Nilius, B.; Zabel, B.; et al. Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy? J. Med. Genet. Part. A 2011, 155, 2860–2864, doi:10.1002/ajmg.a.34268.
  139. Andreucci, E.; Aftimos, S.; Alcausin, M.; Haan, E.; Hunter, W.; Kannu, P.; Kerr, B.; McGillivray, G.; Gardner, R.M.; Patricelli, M.G.; et al. TRPV4 related skeletal dysplasias: A phenotypic spectrum highlighted byclinical, radiographic, and molecular studies in 21 new families. Orphanet J. Rare Dis. 2011, 6, 37, doi:10.1186/1750-1172-6-37.
  140. Vlam, L.; Schelhaas, H.J.; van Blitterswijk, M.; van Vught, P.W.; de Visser, M.; van der Kooi, A.J.; et al. Mutations in the TRPV4 gene are not associated with sporadic progressive muscular atrophy. Neurol. 2012, 69, 790–791.
  141. Chen, D.-H.; Sul, Y.; Weiss, M.; Hillel, A.; Lipe, H.; Wolff, J.; Matsushita, M.; Raskind, W.; Bird, T. CMT2C with vocal cord paresis associated with short stature and mutations in the TRPV4 gene. Neurology 2010, 75, 1968–1975, doi:10.1212/wnl.0b013e3181ffe4bb.
  142. Zimoń, M.; Baets, J.; Auer-Grumbach, M.; Berciano, J.; Garcia, A.; Lopez-Laso, E.; Merlini, L.; Hilton-Jones, D.; McEntagart, M.; Crosby, A.H.; et al. Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies. Brain 2010, 133, 1798–1809, doi:10.1093/brain/awq109.
  143. Wu, Y.; Qi, J.; Wu, C.; Rong, W. Emerging roles of the TRPV4 channel in bladder physiology and dysfunction. Physiol. 2021, 599, 39–47, doi:10.1113/jp279776.
  144. Deng, H.-X.; Klein, C.J.; Yan, J.; Shi, Y.; Wu, Y.; Fecto, F.; Yau, H.-J.; Yang, Y.; Zhai, H.; Siddique, N.; et al. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Genet. 2009, 42, 165–169, doi:10.1038/ng.509.
  145. McEntagart, M. TRPV4 axonal neuropathy spectrum disorder. Clin. Neurosci. 2012, 19, 927–933, doi:10.1016/j.jocn.2011.12.003.
  146. Bird, T.D. Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview; Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Stephens, K., et al., ; GeneReviews((R)): Seattle, WA, USA, 1993.
  147. Landouré, G.; Zdebik, A.A.; Martinez, T.L.; Burnett, B.G.; Stanescu, H.C.; Inada, H.; Shi, Y.; Taye, A.A.; Kong, L.; Munns, C.H.; et al. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Genet. 2009, 42, 170–174, doi:10.1038/ng.512.
  148. Auer-Grumbach, M.; Olschewski, A.; Papić, L.; Kremer, H.; McEntagart, M.E.; Uhrig, S.; Fischer, C.; Froehlich, E.; Bálint, Z.; Tang, B.; et al. Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Genet. 2009, 42, 160–164, doi:10.1038/ng.508.
  149. Fiorillo, C.; Moro, F.; Brisca, G.; Astrea, G.; Nesti, C.; Bálint, Z.; Olschewski, A.; Meschini, M.C.; Guelly, C.; Auer-Grumbach, M.; et al. TRPV4 mutations in children with congenital distal spinal muscular atrophy. Neurogenetics 2012, 13, 195–203, doi:10.1007/s10048-012-0328-7.
  150. Astrea, G.; Brisca, G.; Fiorillo, C.; Valle, M.; Tosetti, M.; Bruno, C.; Santorelli, F.M.; Battini, R. Muscle MRI in TRPV4-related congenital distal SMA. Neurology 2012, 78, 364–365, doi:10.1212/wnl.0b013e318245295a.
  151. Landouré, G.; Sullivan, J.M.; Johnson, J.O.; Munns, C.H.; Shi, Y.; Diallo, O.; Gibbs, J.R.; Gaudet, R.; Ludlow, C.L.; Fischbeck, K.H.; et al. Exome sequencing identifies a novel TRPV4 mutation in a CMT2C family. Neurology 2012, 79, 192–194, doi:10.1212/wnl.0b013e31825f04b2.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Feedback