Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2

Delany, Natalie S.; Hurle, Michael; Facer, P.; Alnadaf, Tanja; Plumpton, Christopher; Kinghorn, Ian; See, Chee Gee; Costigan, Michael; Anand, Praveen; Woolf, Clifford J.; Crowther, Daniel; Sanséau, Philippe; Tate, Simon

doi:10.1152/physiolgenomics.2001.4.3.165

Cited by 224 publications

(164 citation statements)

References 29 publications

(36 reference statements)

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“…Organs-According to Northern blot analysis, TRPV4 is rich in the kidney and lung, and precise detection by antibody or RT-PCR reveals its presence in various other organs than kidney and lung (7,9). TRPV4 protein was analyzed histologically using Western blot analysis with antibody raised against the C terminus.…”

Section: Trpv4 Is Distributed In Various Sensorymentioning

confidence: 99%

“…A clue to its identity came from the discovery of Osm-9 in a genetic screen of highosmolarity-insensitive Caenorhabditis elegans mutants (3). The structure of Osm-9 is quite similar to the vanilloid-receptive channel, VR1 (TRPV1) (4), as well as to TRPV4 (SAC1 (5), OTRPC4 (6), VR-OAC (7), VRl2 (8,9)), and TRPV2 (10). TRPV1 is a member of the TRP family; it has six transmembrane segments and ankyrin-like repeats and is responsive to the physical factor of heat.…”

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confidence: 99%

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Impaired Pressure Sensation in Mice Lacking TRPV4

Suzuki

Mizuno

Kodaira³

et al. 2003

Journal of Biological Chemistry

651

488

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The sensation of pressure, mechanosensation, in vertebrates remains poorly understood on the molecular level. The ion channel TRPV4 is in the TRP family and is a candidate for a mechanosensitive calcium-permeable channel. It is located in dorsal root ganglia. In the present study, we show that disrupting the Trpv4 gene in mice markedly reduced the sensitivity of the tail to pressure and acidic nociception. The threshold to noxious stimuli and the conduction velocity of myelinated nerve responding to stimuli were also impaired. Activation of unmyelinated nerve was undetected. However, the mouse still retained olfaction, taste sensation, and heat avoidance. The TRPV4 channel expressed in vitro in Chinese hamster ovary cells was opened by low pH, citrate, and inflation but not by heat or capsaicin. These data identify the TRPV4 channel as essential for the normal detection of pressure and as a receptor of the high-threshold mechanosensory complex.

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Section: Trpv4 Is Distributed In Various Sensorymentioning

confidence: 99%

mentioning

confidence: 99%

Impaired Pressure Sensation in Mice Lacking TRPV4

Suzuki

Mizuno

Kodaira³

et al. 2003

Journal of Biological Chemistry

651

488

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“…Taken together, these data suggest that PACSIN 3 acts as an auxiliary protein of TRPV4 channel that not only affects the channel's subcellular localization but also modulates its function in a stimulus-specific manner. TRPV4 2 is a Ca 2ϩ -and Mg 2ϩ -permeable non-selective cation channel of the vanilloid-type transient receptor potential (TRPV) channel subfamily (1)(2)(3)(4)(5)(6)(7). Like other TRP channels, it has six transmembrane-spanning (TM) domains with a putative pore region between TM5 and TM6, and cytoplasmic N and C termini (8,9).…”

mentioning

confidence: 99%

Stimulus-specific Modulation of the Cation Channel TRPV4 by PACSIN 3

D’hoedt

Owsianik

Prenen

et al. 2008

Journal of Biological Chemistry

113

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TRPV4, a member of the vanilloid subfamily of the transient receptor potential (TRP) channels, is activated by a variety of stimuli, including cell swelling, moderate heat, and chemical compounds such as synthetic 4␣-phorbol esters. TRPV4 displays a widespread expression in various cells and tissues and has been implicated in diverse physiological processes, including osmotic homeostasis, thermo-and mechanosensation, vasorelaxation, tuning of neuronal excitability, and bladder voiding. The mechanisms that regulate TRPV4 in these different physiological settings are currently poorly understood. We have recently shown that the relative amount of TRPV4 in the plasma membrane is enhanced by interaction with the SH3 domain of PACSIN 3, a member of the PACSIN family of proteins involved in synaptic vesicular membrane trafficking and endocytosis. Here we demonstrate that PACSIN 3 strongly inhibits the basal activity of TRPV4 and its activation by cell swelling and heat, while leaving channel gating induced by the synthetic ligand 4␣-phorbol 12,13-didecanoate unaffected. A single proline mutation in the SH3 domain of PACSIN 3 abolishes its inhibitory effect on TRPV4, indicating that PACSIN 3 must bind to the channel to modulate its function. In line herewith, mutations at specific proline residues in the N terminus of TRPV4 abolish binding of PACSIN 3 and render the channel insensitive to PACSIN 3-induced inhibition. Taken together, these data suggest that PACSIN 3 acts as an auxiliary protein of TRPV4 channel that not only affects the channel's subcellular localization but also modulates its function in a stimulus-specific manner.TRPV4 2 is a Ca 2ϩ -and Mg 2ϩ -permeable non-selective cation channel of the vanilloid-type transient receptor potential (TRPV) channel subfamily (1-7). Like other TRP channels, it has six transmembrane-spanning (TM) domains with a putative pore region between TM5 and TM6, and cytoplasmic N and C termini (8,9). TRPV4 is expressed in a broad range of tissues, including the lung, spleen, testis, fat, brain, cochlea, skin, smooth muscle, kidney, liver, and vascular endothelium (1, 2, 10 -12). Due to its broad expression pattern and gating promiscuity, TRPV4 has the potential to play a role in diverse physiological processes (13). Indeed, using knockdown or knock-out strategies, a role for TRPV4 in osmotic homeostasis, thermosensing, pain, and vascular function has been firmly established (14 -19). However, little is known about the mechanisms that regulate TRPV4 function in these different physiological settings, and it is unclear whether all known activation mechanisms are operating in every TRPV4-expressing cell. Heterologously expressed TRPV4 can be activated by a broad range of physical and chemical stimuli, including osmotic cell swelling (1, 2, 4, 20, 21), moderate heat (12, 22), synthetic ligands stimuli as 4␣-phorbol 12,13-didecanoate (4␣-PDD) (13, 23), mechanical force (14, 19, 24 -26), fluid viscosity (27), and endogenous ligands such as anandamide and arachidonic acid (AA)-derived epo...

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“…TRPV3 is most abundantly expressed on epidermal keratinocytes; yet, it was also described on sensory neurons in co-expression with TRPV1 [273][274][275][276]. TRPV4 was originally described as an osmoreceptor expressed in various tissues including sensory neurons [277][278][279][280] and keratinocytes [281].…”

Section: Trpv3 and Trpv4mentioning

confidence: 99%

TRP Channels and Pruritus

Tóth¹,

Bı́ró²

2013

TOPAINJ

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Itch (pruritus) is one of the most often seen sensory phenomena in clinical practice. Recent neurophysiological findings proposed the existence of a novel pruriceptive system which includes a multitude of pruritogenic (itch-inducing) peripheral mediators, itch-selective pruriceptors, sensory afferent networks, spinal cord neurons, and certain central nervous system regions. In this review, we first introduce major features of the pruriceptive system. We then focus on defining the roles of transient receptor potential (TRP) ion channels in skin-coupled itch and provide compelling evidence that certain thermosensitive TRP channels (especially TRPV1, TRPV3, TRPV4, and TRPA1) are indeed key players in pruritus pathogenesis. Finally, we propose TRP-centered future experimental directions towards the therapeutic targeting of TRP channels in the clinical management of itch.

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Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2

Cited by 224 publications

References 29 publications

Impaired Pressure Sensation in Mice Lacking TRPV4

Impaired Pressure Sensation in Mice Lacking TRPV4

Stimulus-specific Modulation of the Cation Channel TRPV4 by PACSIN 3

TRP Channels and Pruritus

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