Recombinant Mouse Transient receptor potential cation channel subfamily V member 4 (Trpv4), partial

Function

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)

Subcellular Location

Cell membrane; Apical cell membrane (Multi-pass membrane protein); Cell junction, adherens junction; Cell projection, cilium

Tissue Specificity

Detected in liver, kidney, heart, brain cortex, cerebellum and brainstem (at protein level). Expressed in salivary glands (at protein level) (PubMed:16571723). Expressed in heart, lung, spleen, liver, kidney, brain, skeletal muscle and testis. In the central nervous system, expressed in the lamina terminalis (arched vascular organ and neurons of the subfornical organ), median preoptic area, ventral hippocampal commissure, and ependymal cells of the choroid plexus. In the cochlea, expressed in both inner and outer hair cells, and in marginal cells of the cochlear stria vascularis. Expressed in large neurons of the trigeminal ganglion. In the kidney cortex, strongly expressed by epithelial cells of tubules and much weaker in glomeruli

Subunit

Homotetramer. Interacts with calmodulin (By similarity). Interacts with CTNNB1 (PubMed:20413591). The TRPV4 and CTNNB1 complex can interact with CDH1 (PubMed:20413591). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 (By similarity). Interacts with MAP7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES (PubMed:12538589, PubMed:14517216). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) (PubMed:16627472, PubMed:18174177). Interacts with ITPR3 (By similarity). Interacts with AQP5; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (PubMed:16571723). Interacts with ANO1 (PubMed:24509911). Interacts (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040). Interacts with DDX3X; this interaction is decreased when the channel is activated (By similarity)

• Liedtke W.B. et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. — Cell (2000)
• Wissenbach U. et al. Trp12, a novel Trp related protein from kidney. — FEBS Lett. (2000)
• Strotmann R. et al. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. — Nat. Cell Biol. (2000)
• Suzuki M. et al. Impaired pressure sensation in mice lacking TRPV4. — J. Biol. Chem. (2003)
• Derst C. et al. Cloning of mouse and human vanilloid receptor-like protein 2 (VRL-2). (JUN-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Voets T. et al. Molecular determinants of permeation through the cation channel TRPV4. — J. Biol. Chem. (2002)
• Suzuki M. et al. Microtubule-associated protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4). — J. Biol. Chem. (2003)