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J Biol Chem
2016 May 20;29121:11407-19. doi: 10.1074/jbc.M115.702316.
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The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization.
Krauson AJ, Carattino MD.
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Acid-sensing ion channels (ASICs) are cation-selective proton-gated channels expressed in neurons that participate in diverse physiological processes, including nociception, synaptic plasticity, learning, and memory. ASIC subunits contain intracellular N and C termini, two transmembrane domains that constitute the pore, and a large extracellular loop with defined domains termed the finger, β-ball, thumb, palm, and knuckle. Here we examined the contribution of the finger, β-ball, and thumb domains to activation and desensitization through the analysis of chimeras and the assessment of the effect of covalent modification of introduced Cys at the domain-domain interfaces. Our studies with ASIC1a-ASIC2a chimeras showed that swapping the thumb domain between subunits results in faster channel desensitization. Likewise, the covalent modification of Cys residues at selected positions in the β-ball-thumb interface accelerates the desensitization of the mutant channels. Studies of accessibility with thiol-reactive reagents revealed that the β-ball and thumb domains reside apart in the resting state but that they become closer to each other in response to extracellular acidification. We propose that the thumb domain moves upon continuous exposure to an acidic extracellular milieu, assisting with the closing of the pore during channel desensitization.
Akopian,
A new member of the acid-sensing ion channel family.
2000, Pubmed
Akopian,
A new member of the acid-sensing ion channel family.
2000,
Pubmed Arias,
Amiloride is neuroprotective in an MPTP model of Parkinson's disease.
2008,
Pubmed Babinski,
Molecular cloning and regional distribution of a human proton receptor subunit with biphasic functional properties.
1999,
Pubmed
,
Xenbase Baconguis,
X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.
2014,
Pubmed Baconguis,
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
2012,
Pubmed Bässler,
Molecular and functional characterization of acid-sensing ion channel (ASIC) 1b.
2001,
Pubmed
,
Xenbase Benson,
Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neurons.
2002,
Pubmed Bohlen,
A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain.
2011,
Pubmed
,
Xenbase Bonifacio,
Protonation controls ASIC1a activity via coordinated movements in multiple domains.
2014,
Pubmed
,
Xenbase Chen,
Interaction of acid-sensing ion channel (ASIC) 1 with the tarantula toxin psalmotoxin 1 is state dependent.
2006,
Pubmed
,
Xenbase Chen,
A sensory neuron-specific, proton-gated ion channel.
1998,
Pubmed Coryell,
Restoring Acid-sensing ion channel-1a in the amygdala of knock-out mice rescues fear memory but not unconditioned fear responses.
2008,
Pubmed Cushman,
A conformation change in the extracellular domain that accompanies desensitization of acid-sensing ion channel (ASIC) 3.
2007,
Pubmed Dawson,
Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1.
2012,
Pubmed Della Vecchia,
Gating transitions in the palm domain of ASIC1a.
2013,
Pubmed
,
Xenbase de Weille,
Identification, functional expression and chromosomal localisation of a sustained human proton-gated cation channel.
1998,
Pubmed Diochot,
Black mamba venom peptides target acid-sensing ion channels to abolish pain.
2012,
Pubmed
,
Xenbase Duan,
Extracellular spermine exacerbates ischemic neuronal injury through sensitization of ASIC1a channels to extracellular acidosis.
2011,
Pubmed Duan,
Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity.
2007,
Pubmed Escoubas,
Isolation of a tarantula toxin specific for a class of proton-gated Na+ channels.
2000,
Pubmed
,
Xenbase Frey,
Conformational changes in the lower palm domain of ASIC1a contribute to desensitization and RFamide modulation.
2013,
Pubmed
,
Xenbase Friese,
Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system.
2007,
Pubmed García-Añoveros,
BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels.
1997,
Pubmed Gautam,
Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASIC1a, ASIC2, and ASIC3 subunits.
2013,
Pubmed Gielen,
The desensitization gate of inhibitory Cys-loop receptors.
2015,
Pubmed
,
Xenbase Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed Gründer,
A new member of acid-sensing ion channels from pituitary gland.
2000,
Pubmed
,
Xenbase Guex,
SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
1997,
Pubmed Hu,
Role of acid-sensing ion channel 1a in the secondary damage of traumatic spinal cord injury.
2011,
Pubmed Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed Karlin,
Substituted-cysteine accessibility method.
1998,
Pubmed Krauson,
Independent contribution of extracellular proton binding sites to ASIC1a activation.
2013,
Pubmed
,
Xenbase Kusama,
Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition.
2013,
Pubmed Kusama,
Extracellular chloride modulates the desensitization kinetics of acid-sensing ion channel 1a (ASIC1a).
2010,
Pubmed Langlhofer,
Length of the TM3-4 loop of the glycine receptor modulates receptor desensitization.
2015,
Pubmed Li,
Interaction of the aromatics Tyr-72/Trp-288 in the interface of the extracellular and transmembrane domains is essential for proton gating of acid-sensing ion channels.
2009,
Pubmed
,
Xenbase Li,
Asn415 in the beta11-beta12 linker decreases proton-dependent desensitization of ASIC1.
2010,
Pubmed
,
Xenbase Lingueglia,
Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel.
1995,
Pubmed
,
Xenbase Mazzuca,
A tarantula peptide against pain via ASIC1a channels and opioid mechanisms.
2007,
Pubmed McKinnon,
Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.
2012,
Pubmed
,
Xenbase Meiselbach,
Single expressed glycine receptor domains reconstitute functional ion channels without subunit-specific desensitization behavior.
2014,
Pubmed Passero,
Conformational changes associated with proton-dependent gating of ASIC1a.
2009,
Pubmed
,
Xenbase Passero,
Defining an inhibitory domain in the gamma subunit of the epithelial sodium channel.
2010,
Pubmed
,
Xenbase Price,
Cloning and expression of a novel human brain Na+ channel.
1996,
Pubmed
,
Xenbase Ramaswamy,
Proton-mediated conformational changes in an acid-sensing ion channel.
2013,
Pubmed Roy,
Molecular determinants of desensitization in an ENaC/degenerin channel.
2013,
Pubmed Tolino,
Insights into the mechanism of pore opening of acid-sensing ion channel 1a.
2011,
Pubmed
,
Xenbase Waldmann,
The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans.
1996,
Pubmed Wemmie,
The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.
2002,
Pubmed Wemmie,
Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.
2003,
Pubmed Weng,
Cell type-specific expression of acid-sensing ion channels in hippocampal interneurons.
2010,
Pubmed Wong,
Blocking acid-sensing ion channel 1 alleviates Huntington's disease pathology via an ubiquitin-proteasome system-dependent mechanism.
2008,
Pubmed Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed Yu,
A nonproton ligand sensor in the acid-sensing ion channel.
2010,
Pubmed Zhang,
The structural mechanism of the Cys-loop receptor desensitization.
2013,
Pubmed Ziemann,
The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior.
2009,
Pubmed
