Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 Aug 27;28535:27176-81. doi: 10.1074/jbc.M110.143370.
Show Gene links
Show Anatomy links
Wild-type and brachyolmia-causing mutant TRPV4 channels respond directly to stretch force.
Loukin S
,
Zhou X
,
Su Z
,
Saimi Y
,
Kung C
.
???displayArticle.abstract???
Whether animal ion channels functioning as mechanosensors are directly activated by stretch force or indirectly by ligands produced by the stretch is a crucial question. TRPV4, a key molecular model, can be activated by hypotonicity, but the mechanism of activation is unclear. One model has this channel being activated by a downstream product of phospholipase A(2), relegating mechanosensitivity to the enzymes or their regulators. We expressed rat TRPV4 in Xenopus oocytes and repeatedly examined >200 excised patches bathed in a simple buffer. We found that TRPV4 can be activated by tens of mm Hg pipette suctions with open probability rising with suction even in the presence of relevant enzyme inhibitors. Mechanosensitivity of TRPV4 provides the simplest explanation of its various force-related physiological roles, one of which is in the sensing of weight load during bone development. Gain-of-function mutants cause heritable skeletal dysplasias in human. We therefore examined the brachyolmia-causing R616Q gain-of-function channel and found increased whole-cell current densities compared with wild-type channels. Single-channel analysis revealed that R616Q channels maintain mechanosensitivity but have greater constitutive activity and no change in unitary conductance or rectification.
Andrade,
TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity.
2005, Pubmed
Andrade,
TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity.
2005,
Pubmed
Burke,
Phospholipase A2 structure/function, mechanism, and signaling.
2009,
Pubmed
Camacho,
Dominant TRPV4 mutations in nonlethal and lethal metatropic dysplasia.
2010,
Pubmed
Christensen,
TRP channels in mechanosensation: direct or indirect activation?
2007,
Pubmed
Goldin,
Maintenance of Xenopus laevis and oocyte injection.
1992,
Pubmed
,
Xenbase
Krakow,
Mutations in the gene encoding the calcium-permeable ion channel TRPV4 produce spondylometaphyseal dysplasia, Kozlowski type and metatropic dysplasia.
2009,
Pubmed
Kung,
A possible unifying principle for mechanosensation.
2005,
Pubmed
Köttgen,
TRPP2 and TRPV4 form a polymodal sensory channel complex.
2008,
Pubmed
Lesage,
Molecular and functional properties of two-pore-domain potassium channels.
2000,
Pubmed
Liedtke,
Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor.
2000,
Pubmed
Liedtke,
Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans.
2003,
Pubmed
Liedtke,
Molecular mechanisms of TRPV4-mediated neural signaling.
2008,
Pubmed
Lorenzo,
TRPV4 channel participates in receptor-operated calcium entry and ciliary beat frequency regulation in mouse airway epithelial cells.
2008,
Pubmed
Loukin,
Random mutagenesis reveals a region important for gating of the yeast K+ channel Ykc1.
1997,
Pubmed
,
Xenbase
Loukin,
Hypotonic shocks activate rat TRPV4 in yeast in the absence of polyunsaturated fatty acids.
2009,
Pubmed
Loukin,
Forward genetic analysis reveals multiple gating mechanisms of TRPV4.
2010,
Pubmed
,
Xenbase
Lumpkin,
Mechanisms of sensory transduction in the skin.
2007,
Pubmed
Maroto,
TRPC1 forms the stretch-activated cation channel in vertebrate cells.
2005,
Pubmed
,
Xenbase
Mendoza,
TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress.
2010,
Pubmed
Mizoguchi,
Transient receptor potential vanilloid 4 deficiency suppresses unloading-induced bone loss.
2008,
Pubmed
Nilius,
The TRPV4 channel: structure-function relationship and promiscuous gating behaviour.
2003,
Pubmed
Nilius,
Channelopathies converge on TRPV4.
2010,
Pubmed
Patel,
Lipid and mechano-gated 2P domain K(+) channels.
2001,
Pubmed
Rock,
Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia.
2008,
Pubmed
Strotmann,
OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity.
2000,
Pubmed
Su,
The use of yeast to understand TRP-channel mechanosensitivity.
2009,
Pubmed
Suchyna,
Biophysics and structure of the patch and the gigaseal.
2009,
Pubmed
Suzuki,
Impaired pressure sensation in mice lacking TRPV4.
2003,
Pubmed
Thodeti,
TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling.
2009,
Pubmed
Vriens,
Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4.
2004,
Pubmed
Watanabe,
Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels.
2003,
Pubmed
Zhang,
Calcium-, voltage- and osmotic stress-sensitive currents in Xenopus oocytes and their relationship to single mechanically gated channels.
2000,
Pubmed
,
Xenbase
Zhang,
On the discrepancy between whole-cell and membrane patch mechanosensitivity in Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Zhang,
Mechanically gated channel activity in cytoskeleton-deficient plasma membrane blebs and vesicles from Xenopus oocytes.
2000,
Pubmed
,
Xenbase
Zhou,
The transient receptor potential channel on the yeast vacuole is mechanosensitive.
2003,
Pubmed
