8j1b

Structural highlights

Function

TRPV4_MOUSE Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11094154, PubMed:12093812, PubMed:12538589). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:12093812, PubMed:14691263, PubMed:16368742, PubMed:16571723). Also activated by heat, low pH, citrate and phorbol esters (PubMed:14691263). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (By similarity). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (By similarity). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (PubMed:20413591). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (PubMed:23021218). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (PubMed:23021218). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (PubMed:16571723). Required for normal development and maintenance of bone and cartilage (By similarity). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (By similarity). In neurons of the central nervous system, could play a role in triggering voluntary water intake in response to increased sodium concentration in body fluid (PubMed:27252474).[UniProtKB:Q9HBA0]^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]}

References

1. ↑ Wissenbach U, Bödding M, Freichel M, Flockerzi V. Trp12, a novel Trp related protein from kidney. FEBS Lett. 2000 Nov 24;485(2-3):127-34. PMID:11094154 doi:10.1016/s0014-5793(00)02212-2
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. J Biol Chem. 2002 Sep 13;277(37):33704-10. PMID:12093812 doi:10.1074/jbc.M204828200
3. ↑ Xu H, Zhao H, Tian W, Yoshida K, Roullet JB, Cohen DM. Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation. SRC family kinase-dependent tyrosine phosphorylation of TRPV4 on TYR-253 mediates its response to hypotonic stress. J Biol Chem. 2003 Mar 28;278(13):11520-7. PMID:12538589 doi:10.1074/jbc.M211061200
4. ↑ 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. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):396-401. PMID:14691263 doi:10.1073/pnas.0303329101
5. ↑ Xu H, Fu Y, Tian W, Cohen DM. Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking. Am J Physiol Renal Physiol. 2006 May;290(5):F1103-9. PMID:16368742 doi:10.1152/ajprenal.00245.2005
6. ↑ Liu X, Bandyopadhyay BC, Nakamoto T, Singh B, Liedtke W, Melvin JE, Ambudkar I. 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. 2006 Jun 2;281(22):15485-95. PMID:16571723 doi:10.1074/jbc.M600549200
7. ↑ D'hoedt D, Owsianik G, Prenen J, Cuajungco MP, Grimm C, Heller S, Voets T, Nilius B. Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3. J Biol Chem. 2008 Mar 7;283(10):6272-80. PMID:18174177 doi:10.1074/jbc.M706386200
8. ↑ Köttgen M, Buchholz B, Garcia-Gonzalez MA, Kotsis F, Fu X, Doerken M, Boehlke C, Steffl D, Tauber R, Wegierski T, Nitschke R, Suzuki M, Kramer-Zucker A, Germino GG, Watnick T, Prenen J, Nilius B, Kuehn EW, Walz G. TRPP2 and TRPV4 form a polymodal sensory channel complex. J Cell Biol. 2008 Aug 11;182(3):437-47. PMID:18695040 doi:10.1083/jcb.200805124
9. ↑ Sokabe T, Fukumi-Tominaga T, Yonemura S, Mizuno A, Tominaga M. The TRPV4 channel contributes to intercellular junction formation in keratinocytes. J Biol Chem. 2010 Jun 11;285(24):18749-58. PMID:20413591 doi:10.1074/jbc.M110.103606
10. ↑ Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Boström P, Mepani RJ, Laznik D, Kamenecka TM, Song X, Liedtke W, Mootha VK, Puigserver P, Griffin PR, Clapham DE, Spiegelman BM. TRPV4 is a regulator of adipose oxidative metabolism, inflammation, and energy homeostasis. Cell. 2012 Sep 28;151(1):96-110. PMID:23021218 doi:10.1016/j.cell.2012.08.034
11. ↑ Sakuta H, Nishihara E, Hiyama TY, Lin CH, Noda M. Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET-mediated TRPV4 activation. Am J Physiol Regul Integr Comp Physiol. 2016 Aug 1;311(2):R299-306. PMID:27252474 doi:10.1152/ajpregu.00352.2015