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.
Neuron
2008 May 08;583:362-73. doi: 10.1016/j.neuron.2008.04.012.
Show Gene links
Show Anatomy links
A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating.
Myers BR
,
Bohlen CJ
,
Julius D
.
???displayArticle.abstract???
TRP cation channels function as cellular sensors in uni- and multicellular eukaryotes. Despite intensive study, the mechanisms of TRP channel activation by chemical or physical stimuli remain poorly understood. To identify amino acid residues crucial for TRP channel gating, we developed an unbiased, high-throughput genetic screen in yeast that uncovered rare, constitutively active mutants of the capsaicin receptor, TRPV1. We show that mutations within the pore helix domain dramatically increase basal channel activity and responsiveness to chemical and thermal stimuli. Mutation of corresponding residues within two related TRPV channels leads to comparable effects on their activation properties. Our data suggest that conformational changes in the outer pore region are critical for determining the balance between open and closed states, providing evidence for a general role for this domain in TRP channel activation.
Ahern,
A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels.
2006, Pubmed
Ahern,
A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels.
2006,
Pubmed
Alagem,
The pore helix is involved in stabilizing the open state of inwardly rectifying K+ channels.
2003,
Pubmed
,
Xenbase
Asakawa,
Association of a mutation in TRPV3 with defective hair growth in rodents.
2006,
Pubmed
Bandell,
High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol.
2006,
Pubmed
Caterina,
The capsaicin receptor: a heat-activated ion channel in the pain pathway.
1997,
Pubmed
,
Xenbase
Chatelain,
The pore helix dipole has a minor role in inward rectifier channel function.
2005,
Pubmed
,
Xenbase
Chuang,
The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel.
2004,
Pubmed
,
Xenbase
Chuang,
Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.
2001,
Pubmed
,
Xenbase
Chung,
TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes.
2004,
Pubmed
Chung,
2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3.
2004,
Pubmed
Clapham,
TRP channels as cellular sensors.
2003,
Pubmed
Cordero-Morales,
Molecular determinants of gating at the potassium-channel selectivity filter.
2006,
Pubmed
Dhaka,
Trp ion channels and temperature sensation.
2006,
Pubmed
Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed
Décaillot,
Opioid receptor random mutagenesis reveals a mechanism for G protein-coupled receptor activation.
2003,
Pubmed
Gunthorpe,
Voltage- and time-dependent properties of the recombinant rat vanilloid receptor (rVR1).
2000,
Pubmed
Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase
Hu,
2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3.
2004,
Pubmed
,
Xenbase
Jancsó,
Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones.
,
Pubmed
Jerman,
Characterization using FLIPR of rat vanilloid receptor (rVR1) pharmacology.
2000,
Pubmed
Jones,
Protein secondary structure prediction based on position-specific scoring matrices.
1999,
Pubmed
Jordt,
Lessons from peppers and peppermint: the molecular logic of thermosensation.
2003,
Pubmed
Jordt,
Acid potentiation of the capsaicin receptor determined by a key extracellular site.
2000,
Pubmed
Jordt,
Molecular basis for species-specific sensitivity to "hot" chili peppers.
2002,
Pubmed
Julius,
From peppers to peppermints: natural products as probes of the pain pathway.
,
Pubmed
Jung,
Agonist recognition sites in the cytosolic tails of vanilloid receptor 1.
2002,
Pubmed
,
Xenbase
Kim,
Gain-of-function mutation in TRPML3 causes the mouse Varitint-Waddler phenotype.
2007,
Pubmed
Kohda,
Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties.
2000,
Pubmed
Latorre,
ThermoTRP channels as modular proteins with allosteric gating.
2007,
Pubmed
Lishko,
The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity.
2007,
Pubmed
Liu,
Dynamic rearrangement of the outer mouth of a K+ channel during gating.
1996,
Pubmed
Liu,
Change of pore helix conformational state upon opening of cyclic nucleotide-gated channels.
2000,
Pubmed
,
Xenbase
Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Loukin,
Random mutagenesis reveals a region important for gating of the yeast K+ channel Ykc1.
1997,
Pubmed
,
Xenbase
Lukacs,
Dual regulation of TRPV1 by phosphoinositides.
2007,
Pubmed
,
Xenbase
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
Matta,
Voltage is a partial activator of rat thermosensitive TRP channels.
2007,
Pubmed
Minor,
Transmembrane structure of an inwardly rectifying potassium channel.
1999,
Pubmed
Navarro,
Nonselective and G betagamma-insensitive weaver K+ channels.
1996,
Pubmed
Nilius,
TRP channels in disease.
2007,
Pubmed
Oh,
Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons.
1996,
Pubmed
Ou,
One face of a transmembrane helix is crucial in mechanosensitive channel gating.
1998,
Pubmed
Peier,
A heat-sensitive TRP channel expressed in keratinocytes.
2002,
Pubmed
Prescott,
A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity.
2003,
Pubmed
,
Xenbase
Ryu,
Uncoupling proton activation of vanilloid receptor TRPV1.
2007,
Pubmed
,
Xenbase
Sadja,
Coupling Gbetagamma-dependent activation to channel opening via pore elements in inwardly rectifying potassium channels.
2001,
Pubmed
,
Xenbase
Serrano,
Ion homeostasis during salt stress in plants.
2001,
Pubmed
Smith,
TRPV3 is a temperature-sensitive vanilloid receptor-like protein.
2002,
Pubmed
Su,
Yeast gain-of-function mutations reveal structure-function relationships conserved among different subfamilies of transient receptor potential channels.
2007,
Pubmed
Tombola,
How does voltage open an ion channel?
2006,
Pubmed
Tominaga,
The cloned capsaicin receptor integrates multiple pain-producing stimuli.
1998,
Pubmed
,
Xenbase
Voets,
Molecular determinants of permeation through the cation channel TRPV4.
2002,
Pubmed
Voets,
Outer pore architecture of a Ca2+-selective TRP channel.
2004,
Pubmed
Winter,
Characterization of capsaicin-sensitive neurones in adult rat dorsal root ganglion cultures.
1987,
Pubmed
Wood,
Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture.
1988,
Pubmed
Xiao,
The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active.
2008,
Pubmed
,
Xenbase
Xu,
TRPV3 is a calcium-permeable temperature-sensitive cation channel.
2002,
Pubmed
Xu,
Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice.
2007,
Pubmed
Yeh,
Conformational changes of pore helix coupled to gating of TRPV5 by protons.
2005,
Pubmed
Yellen,
The moving parts of voltage-gated ion channels.
1998,
Pubmed
Yi,
Yeast screen for constitutively active mutant G protein-activated potassium channels.
2001,
Pubmed
,
Xenbase
Zhou,
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.
2001,
Pubmed
Zhou,
Yeast screens show aromatic residues at the end of the sixth helix anchor transient receptor potential channel gate.
2007,
Pubmed
